What is Gonad?

The gonad is the organ that makes gametes.

The gonads in males are the testes and the

gonads in females are the ovaries.

The product, gametes, are haploid germ

cells. For example, spermatozoon and egg

cells are gametes.

The presence of the SRY (Sex-determining

region Y) gene, located on the Y chromosome

and encoding the testeis determining factor,

determines male sexual differentiation.

Reproduction – hormones of the

reproductive system

Brain-hypothalamic hormones

Gonadotropin-releasing hormone

(GnRH or LHRH).

Gonadotropin release-inhibitory

factors (GnRIF; such as dopamine)

Pituitary hormones: Gonadotropins

Follicle-stimulating Hormone (FSH):

controls gonadal growth

Luteinizing Hormone (LH): controls

gamete maturation and release

Gonadal hormones (steroids)

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

Gonads & Hormones

GonadalHormone in Male Gonadal Hormone in Female

Ovulation and Corpus Luteum formation Luteinizing hormone (LH)

In males, where LH had also been called

interstitial cell-stimulating hormone (ICSH), it

stimulates Leydig cell production of

testosterone.

Hormone produced by the anterior pituitary

gland

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).

Genes

The gene for the alpha subunit is located on

chromosome 6q12.21.

The LH beta subunit gene is localized in the

LHB/CGB gene cluster on chromosome

19q13.32.

In contrast to the alpha gene activity, beta LH

subunit gene activity is restricted to the pituitary

gonadotropic cells. It is regulated by the

gonadotropin-releasing hormone from the

hypothalamus.

Activity

In both males and females, LH is essential for

reproduction.

In the male, LH acts upon the Leydig cells of the

testis and is responsible for the production of

testosterone, an androgen that exerts both

endocrine activity and intratesticular activity on

spermatogenesis.

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).

In females, LH supports theca cells in the ovary that provide androgens and hormonal precursors for estradiolproduction.

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.

Secretion

pattern of LH

Follicle-stimulating hormone (FSH)

FSH and luteinizing hormone (LH) act

synergistically in reproduction. Specifically, an

increase in FSH secretion by the anterior

pituitary causes ovulation.

It is synthesized and secreted by

gonadotrophs of the anterior pituitary gland.

FSH regulates the development, growth,

pubertal maturation, and reproductive

processes of the body.

FSH is a glycoprotein. Each monomeric unit is a

protein molecule with a sugar attached to it; two of

these make the full, functional protein.

Its structure is similar to those of LH, TSH, and

hCG.

The protein dimer contains 2 polypeptide units,

labeled alpha and beta subunits. The alpha

subunits of LH, FSH, TSH, and hCG are identical,

and contain 92 amino acids. The beta subunits

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.

Structure

Activity

FSH regulates the development, growth, pubertal maturation, and reproductive processes of the

human body.

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 males

FSH stimulates primary spermatocytes to undergo the first division of meiosis, to form

secondary spermatocytes.

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.

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.

Testosterone

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.

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.

Regulation of Testosterone Biosynthesis

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

Estriol

Estradiol

Estrone

They are the primary female sex hormones.

Like all steroid hormones, estrogens readily diffuse across the cell membrane. Once inside

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

During menopause, estrone is the predominant circulating estrogen

during pregnancy estriol is the predominant circulating estrogen

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 is also stored in adipose (fat) tissue.

Progesterone

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.

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.

HORMONAL REGULATION IN NONPREGNANT FEMALE

(UTERINE CYCLE)