Progesterone

This article presents an up-to-date review of the literature on hormone augmentation in the elderly to help primary care physicians better evaluate and utilize hormone replacement and optimization strategies to benefit their patients. The scientific literature suggests that hormone supplementation with estrogen, progesterone, testosterone, growth hormone, and thyroid hormone has the potential to improve quality of life and to prevent, or reverse, the many symptoms and conditions associated with aging, including fatigue, depression, weight gain,frailty, osteoporosis, loss of libido, and heart disease. Possible long-term side effects are also considered.

The role of dopaminergic systems in the control of sexual behavior has been a subject of study for at least 40 years. Not surprisingly, reviews of the area have been published at variable intervals. However, the earlier reviews have been summaries of published research rather than a critical analysis of it. They have focused upon the conclusions presented in the original research papers rather than on evaluating the reliability and functional significance of the data reported to support these conclusions. During the last few years, important new knowledge concerning dopaminergic systems and their behavioral functions as well as the possible role of these systems in sexual behavior has been obtained. For the first time, it is now possible to integrate the data obtained in studies of sexual behavior into the wider context of general dopaminergic functions. To make this possible, we first present an analysis of the nature and organization of sexual behavior followed by a summary of current knowledge about the brain structures of crucial importance for this behavior. We then proceed with a description of the dopaminergic systems within or projecting to these structures. Whenever possible, we also try to include data on the electrophysiological actions of dopamine. Thereafter, we proceed with analyses of pharmacological data and release studies, both in males and in females. Consistently throughout this discussion, we make an effort to distinguish pharmacological effects on sexual behavior from a possible physiological role of dopamine. By pharmacological effects, we mean here drug-induced alterations in behavior that are not the result of the normal actions of synaptically released dopamine in the untreated animal. The conclusion of this endeavor is that pharmacological effects of dopaminergic drugs are variable in both males and females, independently of whether the drugs are administered systemically or intracerebrally. We conclude that the pharmacological data basically reinforce the notion that dopamine is important for motor functions and general arousal. These actions could, in fact, explain most of the effects seen on sexual behavior. Studies of dopamine release, in both males and females, have focused on the nucleus accumbens, a structure with at most a marginal importance for sexual behavior. Since accumbens dopamine release is associated with all kinds of events, aversive as well as appetitive, it can have no specific effect on sexual behavior but promotes arousal and activation of non-specific motor patterns. Preoptic and paraventricular nucleus release of dopamine may have some relationship to mechanisms of ejaculation or to the neuroendocrine consequences of sexual activity or they can be related to other autonomic processes associated with copulation. There is no compelling indication in existing experimental data that dopamine is of any particular importance for sexual motivation. There is experimental evidence showing that it is of no importance for sexual reward.

Recent experimental evidence indicates that progesterone (PROG) protects against various models of brain injury, including ischemic stroke. Most human studies of pharmacologic treatments for acute cerebral stroke have failed despite initial success in animal models. To simulate better the typical human stroke without reperfusion, the present study was conducted to examine the efficacy of PROG on infarct volume and functional outcome in a permanent model of stroke, using direct cauterization of the middle cerebral artery (MCA). Twenty-four male adult Sprague-Dawley rats underwent pMCAO by electro-coagulation and sham operation. After induction of permanent MCA occlusion (pMCAO), the rats received an initial intraperitoneal injection of PROG (8 mg/kg) or vehicle at 1h post-occlusion followed by subcutaneous injections at 6, 24 and 48 h. Functional deficits were tested on the rotarod and grip strength meter at 24, 48 and 72 h after pMCAO. The rats were killed 72 h after surgery and isolated brain was sectioned into coronal slices and stained with 2, 3, 5triphenyltetrazolium chloride (TTC). PROG-treated rats showed a substantial reduction (54.05%) in the volume of the infarct (% contralateral hemisphere) compared to vehicle controls. In addition there was a significant improvement in ability to remain on an accelerating rotarod and increased grip strength observed in the pMCAO rats treated with PROG compared to vehicle. Taken together, these data indicate that PROG is beneficial in one of the best-characterized models of stroke, and may warrant further testing in future clinical trials for human stroke.

We tested the hypothesis that the phosphatidylinositol-3 kinase (PI3K/Akt) pathway mediates some of the neuroprotective effects of progesterone (PROG) after ischemic stroke. We examined whether PROG acting through the PI3K/Akt pathway could affect the expression of vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF). Rats underwent permanent focal cerebral ischemia (pMCAO) by electro-coagulation and received intraperitoneal injections of PROG (8mg/kg) or vehicle at 1h post-occlusion and subcutaneous injections at 6, 24, and 48h. PAkt/Akt levels, apoptosis and apoptosis-related proteins (pBAD, BAD, caspase-3, and cleaved caspase-3) were analyzed by TUNEL assays, Western blotting and immunohistochemistry at 24h post-pMCAO. VEGF and BDNF were analyzed at 24, 72h and 14 days post-pMCAO with Western blots. Following pMCAO, PROG treatment significantly (p<0.05) reduced ischemic lesion size and edema. Treatment with PROG significantly (p<0.05) decreased VEGF at 24 and 72h but increased VEGF expression 14d after injury. The treatment also increased BDNF, and attenuated apoptosis by increasing Akt phosphorylation compared to vehicle-alone. The selective PI3K inhibitor Wortmannin compromised PROG-induced neuroprotective effects and reduced the elevation of pAkt levels in the ischemic penumbra. Our findings lead us to suggest that the PI3K/ Akt pathway can play a role in mediating the neuroprotective effects of PROG after stroke by altering the expression of trophic factors in the brain.

Objective: To assess whether there is an association between the level of progesterone on the day of administration of human chorionic gonadotropin and clinical and laboratory characteristics, in addition to the results of in vitro fertilization of patients with a good prognosis. Methods: A cross-sectional study comprising 103 women who underwent intracytoplasmic sperm injection treatment, between November 2009 and May 2015, aged ≤35 years, with no comorbidities, with fresh embryo transfer. Data were collected from patient medical records. Results: There was a weak positive correlation between the level of progesterone on the day of human chorionic gonadotropin and the number of follicles larger than 14mm (ß=0.02, p=0.001), retrieved oocytes (ß=0.01, p=0.01) and oocytes in metaphase II (MII) (ß=0.02, p=0.02); that is, the increase in progesterone level has a slight association with increased values of these variables. Body mass index was inversely correlated with progesterone level on the day of human chorionic gonadotropin (ß=-0.01, p=0.02). No association was found between the level of progesterone on the day of human chorionic gonadotropin and the protocols used for controlled ovarian stimulation, quality of transferred embryos and the pregnancy rate. Conclusion: There is an association between the value of progesterone on the day of human chorionic gonadotropin administration with body mass index, number of follicles larger than 14mm, number of retrieved oocytes and oocytes in metaphase II. Unlike embryo quality and pregnancy rate, which do not have a statistically significant relation with this value in the population studied.

The objective of this study was to examine relationships among metabolic and endocrine factors that may influence ovarian activity during early lactation. Holstein cows (n = 19) were bled twice each week to determine plasma concentrations of insulin (INS), glucose, cholesterol, insulin-like growth factor-1 (IGF-I), and progesterone (P 4). Feed intake and milk production were recorded daily while body weights and milk composition were recorded weekly. Relationships among plasma cholesterol and P 4 , and days to first and second postpartum ovulation were modeled with energy balance (EB), dry matter intake, milk yield and composition, plasma metabolites, and hormones using the backward elimination technique of multivariate regression analysis. Variables that contributed the most to predicting plasma cholesterol concentrations were dry matter intake × SNF using model 1 (production variables) and the square of glucose (i.e., glucose 2) using model 3 (plasma hormones and metabolites). For plasma P 4 concentrations, EB (model 2, production variables) and IGF-I (model 3, plasma hormones and metabolites) were the major predictors. The production variables EB and percentage of milk lactose were the greatest contributors to the models predicting days to first and second postpartum ovulations, respectively. Of the plasma hormones and metabolites evaluated, IGF-I 2 was the most significant predictor of days to first postpartum ovulation, whereas glucose 2 and INS were the significant predictors of days to second postpartum ovulation. Plasma IGF-I, glucose, and INS have been implicated in ovarian functions and their significant contributions to these models are consistent with possible important roles in postpartum return to ovarian competence.

This study examined the role of pregnancy-induced changes in wakefulness (or nonchemoreflex) and central chemoreflex drives to breathe, acid-base balance and female sex hormones in the hyperventilation of human pregnancy. Thirty-five healthy women were studied in the third trimester (TM 3 ; 36.3 ± 1.0 wks gestation; mean ± SD) and again 20.2 ± 7.8 wks postpartum (PP). An iso-oxic hyperoxic rebreathing procedure was used to evaluate wakefulness and central chemoreflex drives to breathe. At rest, arterialized venous blood was obtained for the estimation of arterial PCO 2 (PaCO 2 ) and [H + ]. Blood for the determination of plasma strong ion difference ([SID]), albumin ([Alb]), as well as serum progesterone ([P 4 ]) and 17-estradiol ([E 2 ]) concentrations was also obtained at rest. Wakefulness and central chemoreflex drives to breathe, [P 4 ] and [E 2 ], ventilation and V · CO 2 increased, whereas PaCO 2 and the central chemoreflex ventilatory recruitment threshold for PCO 2 (VRTCO 2 ) decreased from PP to TM 3 (all p<0.01). The reductions in PaCO 2 were not related to the increases in [P 4 ] and [E 2 ]. The alkalinizing effects of reductions in PaCO 2 and [Alb] were partly offset by the acidifying effects of a reduced [SID], such that arterial [H + ] was still reduced in TM 3 vs. PP (all p<0.001). A mathematical model of ventilatory control demonstrated that pregnancy-induced changes in wakefulness and central chemoreflex drives to breathe, acid-base balance, V · CO 2 and cerebral blood flow account for the reductions in PaCO 2 , [H + ] and VRTCO 2 . This is the first study to demonstrate that the hyperventilation and attendant hypocapnia/alkalosis of human pregnancy results from a complex interaction of pregnancy-induced changes in wakefulness and central chemoreflex drives to breathe, acid-base balance, metabolic rate and cerebral blood flow.

The recent discovery of three closely related cell surface receptors that bind to progesterone and mediate its actions on various cytoplasmic signalling cascades has been heralded as a major break-through. The reason for this is all too obvious. Progesterone is an essential regulator of all major reproductive events and progestins and antiprogestins are widely used in the treatment of many different gynaecological and obstetrical disorders. The novel membrane progestin receptors (mPRalpha, beta, gamma) reportedly resemble and function as G-protein-coupled receptors and therefore are promising pharmaceutical targets. However, our studies failed to corroborate that mPRs are expressed on the cell surface, that they mediate rapid progesterone signalling events, and even that they are bona fide progestin binding moieties. While the reason for these startling opposing results remains unclear, a critical review of existing data may help to shed some light onto the controversial mPRs. Time has come to talk.

The role of gonadal hormones on pain sensations was investigated in normally menstruating women ( n = 16) using the cold pressor test. Tolerance time, pain threshold, and pain intensity were examined once a week during a 4-wk period, and serum concentrations of 17β-estradiol and progesterone were determined at each test session, which were classified into the early follicular phase, late follicular phase, early luteal phase, and late luteal phase, as determined by the first day of menses and the actual hormone levels recorded. A group of men ( n = 10) of the same age interval was examined for comparison. The data show that pain threshold was reduced during the late luteal phase compared with the late follicular phase, and hormone analyses showed significant positive correlation between the progesterone concentration and lowered pain threshold and increasing pain intensity. Hormone analysis also showed an interaction between S-estradiol and S-progesterone on pain intensity, demonstra...

The trend of increasing cow numbers per husbandry person makes it difficult to achieve good reproductive management by traditional means. A system to predict the reproductive status of cows would be of great value. There exist time-series models for detecting oestrus from milk traits other than progesterone and decision strategies for interpreting progesterone measures have been suggested but a system combining these aspects to predict not just oestrus but reproductive status throughout the reproductive cycle is lacking. The objective of this study was to develop such a model on the basis of automated milk progesterone sampling.

The product of meal number x meal size, over time, is food intake. Because estrogens modulate feeding activity via their action on the hypothalamus, and because there is a diurnal rhythm in the expression of cytoplasmic estrogen receptors and in estrogen binding activity, the present study examined the effects of ovariectomy and later hormone therapy on acute changes in body weight, and on the meal number-to-meal size relationship as reflected by food intake in the dark/light feeding patterns, in adult female rats in the intact state and after ovariectomy. Twelve female Fischer rats were randomized into ovariectomy and sham operation groups. A rat eater meter measured the feeding indexes for 15 days before and 25 days after ovariectomy, and later for 35 days with hormone therapy. We report: (a) mean body weight gain was linear before and up to ovariectomy, while exponential after ovariectomy; (b) increase in daily food consumption is mainly via an increase in food intake during the ...

In recent years there has been a growing body of clinical and laboratory evidence demonstrating the neuroprotective effects of estrogen and progesterone after traumatic brain injury (TBI) and spinal cord injury (SCI). In humans, women have been shown to have a lower incidence of morbidity and mortality after TBI compared with age-matched men. Similarly, numerous laboratory studies have demonstrated that estrogen and progesterone administration is associated with a mortality reduction, improvement in neurological outcomes, and a reduction in neuronal apoptosis after TBI and SCI. Here, we review the evidence that supports hormone-related neuroprotection and discuss possible underlying mechanisms. Estrogen and progesterone-mediated neuroprotection are thought to be related to their effects on hormone receptors, signaling systems, direct antioxidant effects, effects on astrocytes and microglia, modulation of the inflammatory response, effects on cerebral blood flow and metabolism, and effects on mediating glutamate excitotoxicity. Future laboratory research is needed to better determine the mechanisms underlying the hormones' neuroprotective effects, which will allow for more clinical studies. Furthermore, large randomized clinical control trials are needed to better assess their role in human neurodegenerative conditions.

The aim of this study was to evaluate the effect of progesterone supplementation and stage of oestrous cycle on in vitro maturation (IVM) of canine oocytes. Oocytes were cultured in medium supplemented with 0, 2000, 4000 or 8000 ng progesterone ml(-1) (Expt 1; n=274 oocytes) or 0, 20, 200 or 2000 ng progesterone ml(-1) (Expt 2; n=789 oocytes). In Expt 3, oocytes (n=1202) were cultured in a bi-phasic system of meiotic arrest followed by IVM, both in the presence of 0, 20, 200 or 2000 ng progesterone ml(-1). Rates of meiotic resumption for Expt 1 ranged from 40.0% to 58.5%; there were no significant differences among groups. In Expt 2, rate of meiotic resumption was significantly lower in the 2000 ng progesterone ml(-1) treatment (35.5%) compared with the 200 ng progesterone ml(-1) treatment (54.0%; P&lt;0.05). There were no significant differences in rates of maturation to metaphase II among treatments in Expt 1 (1.8-8.6%) or Expt 2 (8.4-14.7%); however, oocytes collected from ovarie...

Although dysmenorrhea is a leading cause of gynecologic complaints among adolescents, its pathogenesis is incompletely understood. The purpose of this study was to determine the role of prostaglandins and leukotrienes in the pathogenesis of dysmenorrhea. Twenty patients with dysmenorrhea aged 16.2+/-1.2 years and 20 healthy age-matched controls with eumenorrhea (absence of pain during menstruation) were included in the study. Serial measurements of serum PGF2alpha and urinary LTE4 levels during the menstrual cycle were obtained; serum progesterone was measured and ultrasonographic evaluations were made. LTE4 and PGF2alpha levels decreased on the third day and recovered on the 10th day of the menstrual cycle in both groups. Urinary LTE4 levels were higher in the control group than in the patient group on the 1st, 3rd and 10th days of the cycle (p&lt;0.05 for each). This study suggests that there is a distinct pattern of leukotriene production during the menstrual cycle, but the chang...

Stretched polyethylene (PE) films have been used to orient small molecules for decades by depositing solutions on their surface and allowing the solvent to evaporate leaving the analyte absorbed on the polymer film. However, the non-polar hydrophobic nature of PE is an obstacle to aligning polar molecules and biological samples. In this work PE film was treated with oxygen plasma in order to increase surface hydrophilicity. Different treatment conditions were evaluated using contact angle measurement and X-ray photoelectron spectroscopy. Treated PE (PE OX ) films are shown to be able to align molecules of different polarities including progesterone, 1-pyrenecarboxaldehyde, 4 0 ,6-diamidino-2-phenylindole (DAPI) and anthracene. The degree of alignment of each molecule was studied by running series of linear dichroism (LD) experiments and the polarizations of electronic transition moments were determined. For the first time optimal conditions (such as stretching factor and concentration of the sample) for stretched film LD were determined. PE OX aligning ability was compared to that of normal PE films. Progesterone showed a slightly better alignment on PE OX than PE.

The study investigated the role of odor cues from two nism requiring direct contact with the breeding female. naked mole-rat colonies, in conjunction with behavioral ᭧ 1997 Academic Press cues from nonbreeding colony members, in maintaining suppression of ovulation in subordinate female naked mole-rats isolated from the two parent colonies. Four high ranking nonbreeding female naked mole-rats were Cooperatively breeding, or eusocial, species vary in removed from their respective parent colonies and singly the extent of differential reproductive success among housed in separate burrow systems. For a 64-day period, members in a group ; Sherman, Lathe removed females were maintained in daily odor concey, . In some species, several tact with their parent colony by daily rotating soiled bedindividuals within a single social group breed, resulting ding material between the parent colony and the burrow systems of removed females. In addition, subsets of nonin minimal differences between the reproductive sucbreeding animals from the respective parent colony were cess of group-living individuals (e.g., black-tailed prairegularly moved into the burrow systems of removed rie dogs Cynomys ludovicianus; Hoogland, 1995). In confemales for 2-day periods during this 64-day period. Retrast to this, other species exhibit social systems in moved females were therefore in continual social conwhich reproduction is usually limited to a single inditact with subsets of parent colony animals except for vidual within a sex, resulting in extensive differential the breeding pair. All four removed females exhibited reproductive success between individuals (e.g., insects; raised levels of urinary progesterone (õ 2 ng/mg Cr) in- Wilson, 1971).

The aim of this study was to see whether or not physiological hormonal fluctuations during the menstrual cycle modulate normal aggressiveness in psychophysically healthy women. In 15 probands estrogens (E), progesterone (PROG) and free testosterone (FT) plasma levels were measured by immunochemiluminescence and levels of global aggressiveness and its subitems "verbal aggressiveness", "suspiciousness" and "resentments" were measured by the Buss-Durkee Rating Scale in the early follicular, midluteal and premenstrual phases of the cycle. E and PROG levels varied significantly along the menstrual cycle, while those of FT, of global aggressiveness (GA) and of its subitems did not change. Values of global aggressiveness did not correlate with any of the hormonal parameters studied. However, E values correlated positively with "verbal aggression" scores in the follicular phase and positively with "resentment" in the premenstruum, while PROG levels correlated negatively with "suspiciousness" and "resentment" in the premenstrual phase of the cycle. Hormonal and psychological changes from one phase to the next (Δ) revealed that Δ E in the second half of the cycle correlated negatively with "verbal aggressiveness", while Δ PROG from follicular to luteal and from luteal to premenstrual phases correlated negatively with "resentment". Thus, although aggressiveness did not seem to vary along the menstrual cycle, nor to correlate with hormonal changes, hormone secretions and fluctuations might possibly modulate some of the physiological aspects of the behavioral parameter.

Sixteen multiparous nonpregnant lactating Holstein cows (each weighing 662 { 65 kg in 150.4 { 40 day of lactation) were confined to wooden metabolic cages with 12:12 h light:dark cycle during the experiment. The cows were divided into two sequences of eight cows each and exposed to electric and magnetic fields (EMF) in an exposure chamber. This chamber produced a vertical electric field of 10 kV/m and a uniform horizontal magnetic field of 30 mT at 60 Hz. One sequence was exposed for three estrous cycles of 24 to 27 days. During the first estrous cycle, the electric and magnetic fields were off; during the second estrous cycle, they were on; and during the third estrous cycle, they were off. The second sequence was also exposed for three 24 to 26 days estrous cycles, but the exposure to the fields was reversed (first estrous cycle, on; second estrous cycle, off; third estrous cycle, on). The length of each exposure period (21 to 27 days) varied according to the estrous cycle length. No differences were detected in plasma progesterone concentrations and area under the progesterone curve during estrous cycles between EMF nonexposed and exposed periods (2.28 { 0.17 and 2.25 { 0.17; and 24.5 { 1.9 vs. 26.4 { 1.9 ng/ml, respectively). However, estrous cycle length, determined by the presence of a functional corpus luteum detected by concentrations of progesterone equal to or more than 1 ng/ml plasma, was shorter in nonexposed cows than when they were exposed to EMF (22.0 { 0.9 vs. 25.3 { 1.4 days).

Sixteen multiparous nonpregnant lactating Holstein cows (each weighing 662 { 65 kg in 150.4 { 40 day of lactation) were confined to wooden metabolic cages with 12:12 h light:dark cycle during the experiment. The cows were divided into two sequences of eight cows each and exposed to electric and magnetic fields (EMF) in an exposure chamber. This chamber produced a vertical electric field of 10 kV/m and a uniform horizontal magnetic field of 30 mT at 60 Hz. One sequence was exposed for three estrous cycles of 24 to 27 days. During the first estrous cycle, the electric and magnetic fields were off; during the second estrous cycle, they were on; and during the third estrous cycle, they were off. The second sequence was also exposed for three 24 to 26 days estrous cycles, but the exposure to the fields was reversed (first estrous cycle, on; second estrous cycle, off; third estrous cycle, on). The length of each exposure period (21 to 27 days) varied according to the estrous cycle length. No differences were detected in plasma progesterone concentrations and area under the progesterone curve during estrous cycles between EMF nonexposed and exposed periods (2.28 { 0.17 and 2.25 { 0.17; and 24.5 { 1.9 vs. 26.4 { 1.9 ng/ml, respectively). However, estrous cycle length, determined by the presence of a functional corpus luteum detected by concentrations of progesterone equal to or more than 1 ng/ml plasma, was shorter in nonexposed cows than when they were exposed to EMF (22.0 { 0.9 vs. 25.3 { 1.4 days).

Astroglia and steroid hormones such as estrogen and progesterone regulate cell growth, function, and protection in the central nervous system (CNS). It appears that astrocytes and steroids act in concert to promote cell survival under pathological conditions. With respect to the role of mitochondrial fusion and fission in energy metabolism, apoptosis, and proliferation, astrocyte mitochondria resemble a perfect intracellular target for steroids to modulate these processes, thereby promoting cell vitality after damage. We have studied the effects of estrogen and progesterone on cell viability in comparison with mitochondrial fusion and fission gene transcription in primary cortical astrocytes from female and male mouse brains. Estrogen-and progesterone-treated female astrocytes demonstrated an increase in cell number and proliferation marker accompanied by an upregulation of fusion and fission gene transcription, which were apparently balancing pro-and anti-apoptotic processes. On the other hand, male astrocytes exhibited no change in cell number after estrogen treatment, but a decrease after progesterone administration. This could be the consequence of stimulated apoptosis in male astrocytes by both steroids, which was counterbalanced by an increased proliferation in the presence of estrogen, whereas it was strengthened in the presence of progesterone. Supportively, estrogen promoted and progesterone decreased the transcription of fusion and fission genes. We suggest that estrogen and progesterone affect mitochondrial fusion and fission gene transcription in cortical astrocytes in a gender-specific way, thereby influencing mitochondrial function differently in both genders. Thus, interaction of sex steroids with mitochondria may represent one possible cause for gender differences in cellular pathology in the CNS.

Female green iguanas, Iguana iguana, were caught in Belize, Central America (17"N), in December, at the onset of seasonal gonadal activity. The animals were immediately transferred to San Diego (32"N). Ovarian follicular development continued, with peak plasma hormone levels measured in January and February; 200 pg/ml for progesterone (P) and 800 pg/ml for

Twenty-three parotid and twelve submandibular human salivary glands were used for analyzing in vitro metabolism of progesterone (P) and/or testosterone (T), in order to find out their possible contribution to the concentrations of salivary P or T. Glands were excised from 21 women and 14 men because of a stone, tumor or sialoadenitis, and the healthy tissue was used for incubation. The tissues were homogenized and incubated with 5 to 7 nmol/I of [14C]P or [t4C]T for 2 h, extracted with methylacetate and subjected to two dimensional thin-layer chromatography. The thin-layer plates were autoradiographed, and the radioactivity of the different metabolites were counted to assess the amounts of metabolites formed. No lipoidal or conjugated steroids were formed. All of the radioactivity was associated with the free fraction of steroids. Both P and T were metabolized significantly more actively in male submandibular gland compared to male parotid gland (P <0.05-0.01). No significant differences were found between female and male parotid glands, nor between the parotid glands of hormonally medicated (oral contraceptives or postmenopausal estrogen treatment) and non-medicated women. The submandibular glands more actively metabolized the steroids studied than the parotids (P < 0.01). The main metabolites were 20~t-hydroxy-4 pregnen-3-one for P, and androstenedione for T. In conclusion, the present results bring further evidence that the P or T levels in saliva may not be identical with the unbound steroid fraction in circulation, but a part of the steroids are metabolized in salivary glands. However, due to the rapid passage of steroids from blood to saliva, the metabolism demonstrated probably does not form an important source of error in salivary P and T measurements.

Preeclampsia (PE) affects around 2-5% of pregnant women. It is a major cause of maternal and perinatal morbidity and mortality. In an attempt to prevent preeclampsia, many strategies based on antenatal care, change in lifestyle, nutritional supplementation, and drugs have been studied. The aim of this paper is to review recent evidence about primary and secondary prevention of preeclampsia.

Hair sheep ewes (St. Croix White and Barbados Blackbelly) were used to evaluate 3 methods of estrus synchronization for use with transcervical artificial insemination (TAI). To synchronize estrus, ewes (n = 18) were treated with PGF2¢ (15 mg, im) 10 d apart, with controlled internal drug release (CIDR) devices containing 300 mg progesterone for 12 d (n = 18), or with intravaginal sponges containing 500 mg progesterone for 12 d (n = 18). On the day of the second PGF2a injection or at CIDR or sponge removal, sterile rams were placed with the ewes. jugular blood samples were collected from the ewes at 6-h intervals until the time of ovulation, and daily for 16 d after estrus (Day 0). Plasma was harvested and stored at-20°C until LH, and progesterone concentrations were determined by RIA. There was no difference (P > 0.10) in time to estrus among the CIDR-, PGF2c¢-or sponge-treated ewes. All of the ewes in the CIDR group and 94.4% of the sponge treated ewes exhibited estrus by 36 h after ram introduction, while only 72.2% of PGF2a-treated ewes showed signs of estrus by this time (P < 0.06). The time from ram introduction to ovulation was not different (P > 0.10) among the CIDR-, PGF2c¢-or sponge-treated ewes. The time to the preovulatory LH surge was similar (P > 0.10) among CIDR, PGF2c¢ and sponge treated ewes. Progesterone levels through Day 16 after the synchronized estrus were not different (P > 0.10) among treatment groups. Hair sheep ewes (n = 23) were synchronized using PGF2c¢ and bred by TAI using frozenthawed semen 48 h after the second injection. The conception rate to TAI was 2/23 (8.7%) and produced 3 ram lambs. In a subsequent trial, 17 ewes were synchronized with CIDR devices and bred by TAI using frozen-thawed semen 48 h after CIDR removal, resulting in a conception rate of 52.9 % (9/17). It is possible to synchronize estrus in hair sheep using either CIDRs, sponges or PGF2c¢. Even though there were no significant differences in the timing of ovulation Or the LH surge among the treatment groups, a higher conception rate was achieved in ewes synchronized with CIDR devices during the second trial. This may reflect an increase in the skill level of the TAI technidan.

Different routes of natural progesterone supplementation have been tried as luteal phase support in infertility treatments. Orally administered progesterone is rapidly metabolized in the gastrointestinal tract and its use has proved to be inferior to i.m. and vaginal routes. Progesterone i.m. achieves serum progesterone values that are within the range of luteal phase and results in sufficient secretory transformation of the endometrium and satisfactory pregnancy rates. The comparison between i.m. and vaginal progesterone has led to controversial results as regards the superiority of one or the other in inducing secretory endometrial transformation. However, there is increasing evidence in the literature to favour the use of vaginal progesterone. Vaginally administered progesterone achieves adequate endometrial secretory transformation but its pharmacokinetic properties are greatly dependent on the formulation used. After vaginal progesterone application, discrepancies have been detected between serum progesterone values and histological endometrial features. Vaginally administered progesterone results in adequate secretory endometrial transformation, despite serum progesterone values lower than those observed after i.m. administration, even if they are lower than those observed during the luteal phase of the natural cycle. This discrepancy is indicative of the first uterine pass effect and therefore of a better bioavailability of progesterone in the uterus, with minimal systematic undesirable effects.

The steroidal hormonal proWles of two sympatric species of desert snails, Sphincterochila zonata and Sphincterochila prophetarium were determined at three ecophysiological-behavior stages, i.e., aestivation, cryptobiosis, and active-feeding phases. Live snails were collected in their natural habitat every month for 13 months, the corpi removed and extracted with organic solvents and the progesterone, testosterone, and estrogen concentrations determined by radioimmunoassay. In both these hermaphroditic species during aestivation, a peak of testosterone followed by a peak of estrogen was observed. During the brief active intervals, minor peaks of estrogen were also observed but these were much lower than seen during aestivation. Although the two species have diVerent microhabitats during aestivation, there was little diVerence in the hormonal proWle, although S. prophetarum had about two fold higher progesterone concentration than S. zonata.

The (As) arsenic exposure is a risk factor for causing disturbances in the endocrine organs. Objective: To evaluate if sub-chronic As exposure during the pre-and postnatal development causes disturbances in the puberty. Moreover, determine adverse effects of As on the ovarian follicle and adrenocortical cell maturation. Methods: Females adult Wistar rats were exposed to sodium arsenite at 3 ppm calculated as As in drinking water from mating, gestation. Following the birth, the female offspring continued exposured to As via lactation. Weaned pups received the same As treatment as mothers, until they were 1-4 months (mo) old. At these ages, blood sampling and tissue harvest were done. The tissues were fixed in situ with 4% paraformaldehyde in phosphate buffer. After the perfusion the ovaries, uterus, adrenal glands were harvested, dissected out, weighted. The ovaries and the adrenal glands were processed to paraffin and sectioned at 5 M and stained with hematoxylin and eosin for light microscopy. Statistical analysis: Comparisons between groups were made by unpaired t-test or nonparametric Mann-Whitney test as appropriate. Results: 100% As treated rats at 1 mo of age were at diestrous stage, with low estradiol E2. As treatment caused disturbances in the morphology of the ovarian cell consisting in DNA damage evidenced by picknotic chromatin, cariorexis, significant cytoplasmic vacuolization and also vasculature damaged. Arrest in follicle maturation was also present. Conclusions: We found that the onset of puberty in the As treated rats was 1 mo delayed since vagina was still closed, the vaginal smear showed that they were at diestrus stage with plasma low E2 levels.

Progesterone rapidly dissolves in an aqueous solution containing hydroxypropyl-b-cyclodextrin (HPBCD) at 1:2 molar ratio, forming a soluble inclusion complex. After filtration and freeze-drying of the final solution, the final powder was examined by SEM, DSC, TGA, XRD, Raman, and FTIR spectroscopy. Experimental results confirm that an inclusion complex exists in the solid state and possible structure of the complex is briefly discussed. ß

The relationship between the concentration of plasma progesterone (P4) during embryo attachment or at recognition of pregnancy, and that of pregnancy-associated glycoprotein (PAG) was assessed in dairy cows. The outcome of artificial insemination (AI) was classified as positive (AI+), negative (AIÀ), or late embryonic mortality (EM) by measuring circulating PAG concentrations and by ultrasonography. Based on P4 concentrations at either day 21 or day 15, AI+ and EM cows were classified into 'low' (P4 concentrations < mean) and 'high' (P4 concentrations > mean) P4 groups. In both experiments, the threshold of P4 concentration between the 'low' and 'high' groups was approximately 6 ng/mL. PAG concentrations were lower in the 'low' group only when P4 concentrations were below the threshold. The study findings suggest that a possible P4 threshold exists below which PAG secretion may be impaired.

A case-control study was carried out in Mexico City during 1995–1997 among women with epithelial ovarian cancer (84 cases) and endometrial cancer (85 cases). The control group consisted of 668 healthy women, matched according to age categories. In a multivariate analysis, the ...

Land application of manure may contribute endocrine disrupting compounds (EDCs) such as steroid hormones to the environment. Little attention has been paid to the potential for degradation of steroid hormones by manure-borne bacteria and their degradation kinetics and pathways. In a laboratory study, the potential for biodegradation of testosterone, 17b-estradiol (E2) and progesterone by swine (Sus scrofa) manure-borne bacteria was examined. In addition, the impact of temperature, pH (6, 7, and 7.5), glucose amendments (0, 3, and 22 mmol L -1 ), and presence of oxygen on testosterone degradation kinetics was determined. Testosterone, 17b-estradiol and progesterone were biodegraded within 25 h of reaction initiation under aerobic conditions. The degradation of testosterone followed pseudo first-order and zero-order reaction kinetics under aerobic and anaerobic conditions, respectively, in tryptic soy broth (TSB) pre-enriched systems. The half-life (t 1/2 ) for the degradation of testosterone under anaerobic conditions was six times longer than aerobic conditions. Testosterone degradation was found to significantly increase (~ 17%) when incubated at 37°C vs. 22°C. The impact of pH (t 1/2 ranged from 4.4-4.9 h) and glucose amendments (t 1/2 ranged from 4.6-5.1 h) on the testosterone degradation rate were found to be small. Testosterone was transformed to dehydrotestosterone (DHT) (major degradation product), androstenedione (AD), and androstadienedione (ADD) under aerobic conditions as revealed by liquid chromatography-time-of-flight mass spectrometry (LC/TOF-MS). These results indicate that testosterone is rapidly degraded by manure-borne bacteria under a wide range of environmentally relevant conditions. However, the formed degradation products are still of potential concern due to their endocrine disrupting potential.

Objective: To identify dominant predictors of clinical pregnancy in IVF cycles. Design: Retrospective study. Setting: Private fertility center. Patient(s): The study included 580 fresh autologous IVF cycles with blastocyst transfer. Intervention(s): None. Main Outcome Measure(s): Clinical pregnancy rate.

Validating questionnaires for social pharmacy research with smaller sample sizes can be unnecessarily timeconsuming and costly, a solution to this is cognitive interviewing with 2 interviews per iteration. This paper shows how cognitive interviewing with pairs of interviews per iteration of the questionnaire can be used to identify overt and covert issues with comprehension, retrieval, judgment and response experienced by respondents when attempting to answer a question or navigate around the questionnaire. When used during questionnaire development in small scale social pharmacy research studies cognitive interviewing can reduce both respondent burden and response error and should result in more reliable survey results. The process of cognitive interviewing is illustrated by a case study from the development of the Perspectives on Progesterone questionnaire.

Previously, the presence of a wide variety of chemically diverse steroids has been identified in both flora and fauna. Despite the relatively small differences in chemical structures and large differences in physiological function of steroids, new discoveries indicate that plants and animals are more closely related than previously thought. In this regard, the present study gathers supporting evidence for shared phylogenetic roots of structurally similar steroids produced by these two eukaryotic taxa. Definitive proof for the presence of progesterone (3) in a vascular plant, Juglans regia, is provided. Additional evidence is gleaned from the characterization of five new plant steroids from Adonis aleppica: three 3-O-sulfated pregnenolones , a sulfated H-5 cardenolide, strophanthidin-3-O-sulfate (8), and spirophanthigenin (10), a novel C-18 oxygenated spirocyclic derivative of strophanthidin. The ab initio isolation and structure elucidation (NMR, MS) of these genuine minor plant steroids offers information on preparative metabolomic profiling at the ppm level and provides striking evidence for the conserved structural space of pregnanes and its congeners across the phylogenetic tree.

Objectives This article is aimed to review the novel actions of progesterone, which otherwise is considered as a female reproductive hormone. The article focuses on its important physiological actions in males too and gives an overview of its novel perspectives in disorders of central and peripheral nervous system.

Increased glucose uptake as a principal energy source is a requirement for the continued survival of tumour cells. Facilitative glucose transporter-1 (GLUT1) and -3 (GLUT3) have been previously shown to be present and regulated in breast cancer cells and are associated with poor patient prognosis. In cancer cells, the cAMP secondary messenger pathway is known to potentiate described glucose transporter activators and regulate cell fate. However, no regulation of the glucose transporters in breast cancer cells by cAMP has previously been examined. Herein, we determined in the well-characterized breast cancer cell line ZR-75, if the cAMP analogue 8-br-cAMP was capable of regulating GLUT1 and GLUT3 expression and thus glucose uptake. We demonstrated that 8-br-cAMP transiently up-regulates GLUT3 mRNA levels. The use of actinomycin-D and the cloning of 1,200 bp upstream of the human GLUT3 promoter demonstrated that this regulation was transcriptional. Immunocytochemistry and Western blotting confirmed that the increase in mRNA was reflected by an increase in protein levels. No notable regulation of GLUT1 in the presence of 8-br-cAMP was detected. Finally, we determined using the non-metabolizable glucose analogue 2-DOG if this up-regulation in GLUT3 increased glucose uptake. We observed the presence of two uptake components, one corresponding to the Km of GLUT1/4 and the other to GLUT3. A doubling in the uptake velocity was observed only at the Km corresponding to GLUT3. In conclusion, we demonstrate and characterize for the first time, an upregulation of GLUT3 mRNA, protein and glucose uptake by the cAMP pathway in breast cancer cells.