What is Gonad?

Reproduction – hormones of the

reproductive system
The gonad is the organ that makes gametes.
The gonads in males are the testes and the  Brain-hypothalamic hormones
gonads in females are the ovaries.  Gonadotropin-releasing hormone
(GnRH or LHRH).
The product, gametes, are haploid germ
 Gonadotropin release-inhibitory
cells. For example, spermatozoon and egg
factors (GnRIF; such as dopamine)
cells are gametes.
 Pituitary hormones: Gonadotropins
The presence of the SRY (Sex-determining  Follicle-stimulating Hormone (FSH):
region Y) gene, located on the Y chromosome controls gonadal growth
and encoding the testeis determining factor,  Luteinizing Hormone (LH): controls
determines male sexual differentiation. gamete maturation and release
 Gonadal hormones (steroids)
Gonads & Hormones  11-ketotestosterone (androgen):
important for spermatogenesis
 17-estradiol (estrogen): important for
oogenesis
 Progesterone or its derivatives
(progestins): induce gamete
maturation in males and females and
ovulation in females
 GonadalHormone in Male Gonadal Hormone in Female

Ovulation and Corpus Luteum formation Luteinizing hormone (LH)

Hormone produced by the anterior pituitary
gland
In males, where LH had also been called
interstitial cell-stimulating hormone (ICSH), it
stimulates Leydig cell production of
testosterone.

In females, an acute rise of LH ("LH surge")

triggers ovulation and development of the
corpus luteum
It acts synergistically with FSH.
 Structure of LH
 LH is a heterodimeric glycoprotein.
 Each monomeric unit is a glycoprotein molecule
 One alpha and one beta subunit make the full, functional protein.

 The alpha subunits of LH contain 92 amino acids in human but 96 amino acids in almost all other
vertebrate species. The carbohydrate moiety is linked to the asparagine at positions 52 and 78.

 LH beta subunit have 120 amino acids (LHβ) that confers its specific biologic action and is
responsible for the specificity of the interaction with the LH receptor.

The biologic half-life of LH is 20 minutes, shorter than that of FSH (3–4 hours) and hCG (24
hours).

Activity
Genes
The gene for the alpha subunit is located on In both males and females, LH is essential for
chromosome 6q12.21. reproduction.

The LH beta subunit gene is localized in the  In the male, LH acts upon the Leydig cells of the
LHB/CGB gene cluster on chromosome testis and is responsible for the production of
19q13.32. testosterone, an androgen that exerts both
endocrine activity and intratesticular activity on
In contrast to the alpha gene activity, beta LH spermatogenesis.
subunit gene activity is restricted to the pituitary
gonadotropic cells. It is regulated by the
gonadotropin-releasing hormone from the
hypothalamus.
 In females, LH supports theca cells in the ovary that provide androgens and hormonal precursors for estradiol
production.
At the time of menstruation, FSH initiates follicular growth, specifically affecting granulosa cells.
With the rise in estrogens, LH receptors are also expressed on the maturing follicle, which causes it to produce
more estradiol.
When the follicle has fully matured, a spike in estrogen production by the follicle stimulates a positive feedback
loop in the hypothalamus that stimulates the release of LH from the anterior pituitary.
This increase in LH production only lasts for 24 to 48 hours.
This "LH surge" triggers ovulation, thereby not only releasing the egg from the follicle, but also initiating the
conversion of the residual follicle into a corpus luteum that, in turn, produces progesterone to prepare the
endometrium for a possible implantation.

LH is necessary to maintain luteal function for the first two weeks of the menstrual cycle. If pregnancy occurs, LH levels
will decrease, and luteal function will instead be maintained by the action of hCG (a hormone very similar to LH but
secreted from the new placenta).

Secretion
pattern of LH
 Follicle-stimulating hormone (FSH) Structure
 It is synthesized and secreted by  FSH is a glycoprotein. Each monomeric unit is a
gonadotrophs of the anterior pituitary gland. protein molecule with a sugar attached to it; two of
these make the full, functional protein.
 FSH regulates the development, growth,
pubertal maturation, and reproductive  Its structure is similar to those of LH, TSH, and
processes of the body. hCG.

 The protein dimer contains 2 polypeptide units,

 FSH and luteinizing hormone (LH) act
labeled alpha and beta subunits. The alpha
synergistically in reproduction. Specifically, an
subunits of LH, FSH, TSH, and hCG are identical,
increase in FSH secretion by the anterior
and contain 92 amino acids. The beta subunits
pituitary causes ovulation.
vary. FSH has a beta subunit of 111amino acids
(FSH β), which confers its specific biologic action
and is responsible for interaction with the FSH-
receptor.
 The half-life of FSH is 3–4 hours.

Activity
FSH regulates the development, growth, pubertal maturation, and reproductive processes of the
human body.
Effects in males
 FSH stimulates primary spermatocytes to undergo the first division of meiosis, to form
secondary spermatocytes.

 FSH enhances the production of androgen-binding protein by the Sertoli cells of the testes
by binding to FSH receptors on their basolateral membranes, and is critical for the initiation of
spermatogenesis.
 Effects in females
 FSH stimulates the growth
and recruitment of immature
ovarian follicles in the ovary.

 In early (small) antral

follicles, FSH is the major
survival factor that rescues the
small antral follicles (2–5 mm
in diameter for humans) from
apoptosis (programmed death
of the somatic cells of the
follicle and oocyte).

Gonadotropin-releasing hormone (GnRH),

 Also known as Luteinizing-hormone-releasing hormone (LHRH) and luliberin, is a trophic peptide
hormone responsible for the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
from the anterior pituitary.

 GnRH is synthesized and released from neurons within the hypothalamus.

 GnRH is considered a neurohormone, a hormone produced in a specific neural cell and released
at its neural terminal.

 At the pituitary, GnRH stimulates the synthesis and secretion of the gonadotropins, follicle-
stimulating hormone (FSH), and luteinizing hormone (LH).

 Low-frequency GnRH pulses lead to FSH release, whereas high-frequency GnRH pulses stimulate
LH release.
Gonadal
Steroid
hormones:
 Testosterone

 Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles,
birds, and other vertebrates.

 In mammals, testosterone is primarily secreted in the testicles of males and the ovaries of
females, although small amounts are also secreted by the adrenal glands.

 It is the principal male sex hormone and an anabolic steroid. Testosterone

 In men, testosterone plays a key role in the development of male reproductive tissues such as the
testis and prostate as well as promoting secondary sexual characteristics such as increased muscle,
bone mass, and the growth of body hair.

Biosynthesis of testosterone
 The largest amounts of testosterone (>95%) are produced by the testes in men.

 It is also synthesized in far smaller quantities in women by the thecal cells of the ovaries, and by the
placenta,

 The zona reticularis of the adrenal cortex and skin in both sexes also produces in small quantities.

 In the testes, testosterone is produced by the Leydig cells. The male generative glands also contain
Sertoli cells which require testosterone for spermatogenesis.
 Regulation of Testosterone Biosynthesis
Testosterone is primarily synthesized in Leydig cells.

The number of Leydig cells in turn is regulated by luteinizing

hormone (LH) and follicle stimulating hormone (FSH).

The amount of testosterone produced by existing Leydig cells is

under the control of LH which regulates the expression of 17-β
hydroxysteroid dehydrogenase (HSD).

When testosterone levels are low, gonadotropin-releasing

hormone (GnRH) is released by the hypothalamus which in turn
stimulates the pituitary gland to release FSH and LH. These later
two hormones stimulate the testis to synthesize testosterone.

Finally increasing levels of testosterone through a negative

feedback loop act on the hypothalamus and pituitary to inhibit the
release of GnRH and FSH/LH respectively.

Biosynthesis of Estrogen:

 Estrogens, in females, are produced primarily by the ovaries, and during pregnancy, the placenta.
 Follicle-stimulating hormone (FSH) stimulates the ovarian production of estrogens by the
granulosa cells of the ovarian follicles and corpora lutea.

 Some estrogens are also produced in smaller amounts by other tissues such as the liver,
adrenal glands, and the breasts.

 In females, synthesis of estrogens starts in theca interna cells in the ovary, by the synthesis
of androstenedione from cholesterol.
 Estrogen
They are the primary female sex hormones.

Like all steroid hormones, estrogens readily diffuse across the cell membrane. Once inside Estriol
the cell, they bind to and activate estrogen receptors which in turn modulate the expression
of many genes. Additionally, estrogens have been shown to activate a G protein-coupled
receptor, GPR30.
Estradiol is the predominant estrogen during reproductive years Estradiol

During menopause, estrone is the predominant circulating estrogen

during pregnancy estriol is the predominant circulating estrogen
Estrone
Function of Estrogen
 Promote formation of female secondary sex characteristics

 Accelerate metabolism

 Increase fat stores

 Stimulate endometrial growth

 Increase uterine growth

 Increase vaginal lubrication

 Thicken the vaginal wall

 Maintenance of vessel and skin

 Reduce bone resorption, increase bone formation

 Reduce muscle mass

 Progesterone
 Progesterone also known as P4 (pregn-4-ene-3,20-dione) is a C-21 steroid hormone involved in
the female menstrual cycle, pregnancy and embryogenesis of humans and other species.

 Progesterone belongs to a class of hormones called progestogens, and is the major naturally
occurring human progestogen.

 Progesterone is produced in the ovaries (by the corpus

luteum), the adrenal glands and, during pregnancy, in the
placenta. Progesterone

 Progesterone is also stored in adipose (fat) tissue.

Level of Progesterone
 In women, progesterone
levels are relatively low during
the preovulatory phase of the
menstrual cycle, rise after
ovulation, and are elevated
during the luteal phase, as
shown in diagram below.
 Progesterone levels tend to
be < 2 ng/ml prior to ovulation,
and > 5 ng/ml after ovulation.
 If pregnancy occurs, human
chorionic gonadotropin is
released maintaining the
corpus leuteum allowing it to
maintain levels of
progesterone.
 HORMONAL REGULATION IN NONPREGNANT FEMALE

(UTERINE CYCLE)
 HYPOTHALAMUS RELEASES GONADOTROPIN-RELEASING HORMONE (GnRH). This stimulates the
anterior pituitary to release FSH and LH.
 FSH STIMULATES MATURATION OF PRIMARY OOCYTE IN AN IMMATURE FOLLICLE.
 FOLLICLE PRODUCES ESTROGEN. Estrogen: (A) builds the uterine wall (the endometrium); (B) inhibits
secretion of FSH.
 HIGH LEVELS OF ESTROGEN FURTHER STIMULATE SECRETION OF LH BY ANTERIOR PITUITARY.
This plus FSH also causes ovulation of the secondary oocyte – leaving follicle without egg (the corpus
luteum).
 CORPUS LUTEUM SECRETES ESTROGEN AND PROGESTERONE. This maintains the endometrium
for 15-16 days and inhibits LH.
 (If oocyte is not fertilized and implanted in the uterine wall) CORPUS DEGENERATES (TO CORPUS
ALBICANS) AND STOPS PRODUCING ESTROGEN AND PROGESTERONE.
 WITHOUT ESTROGEN AND PROGESTERONE, ENDOMETRIUM BREAKS DOWN – MENSTRUATION
OCCURS. Menstruation is the sloughing off of the enlarged endometrial wall along with blood and mucous.
 DECREASE IN PROGESTERONE AND LH. Low LH causes secretion of FSH by pituitary again. The
cycle repeats.