According sex, the gonads are : Ovaries (female) secrete: Progesterone prepares the uterus for implantation of fertilized ovum if present. (luteal phase) Estrogen: it has receptors on hypothalamus so it is the end product that can control secretion of HPA axis. Testes (male): the main secretion is testosterone (control secretion of HPA axis)

In females; LH and FSH (estrogen and progesterone) are different according to the period of menstrual cycle. At the first day of cycle, there is low level of estrogen. loss of negative feedback mechanism with increase in LH and FSH.

FSH important for maturation of ovarian follicle and so ovum (follicular phase) LH stimulates secretion of estrogen from developing follicles. This estrogen increases to a very high level leading to peak increase in LH level which is critical for ovulation.

Progesterone: It is a 21C steroid and the Synthetic compounds called 19-nortestosterone is widely used as an oral contraceptive is more potent than prog. Metabolism: production in ovaries occurs by steroidogenesis. In blood, it is bound to CBG. The free level is 10-20% of total, which remains constant throughout the menstrual cycle. Its peak level occurs at luteal phase. It conjugated with glucoronic acid and excreted as water-soluble substance in urine called pregnenidiol. This is used clinically as index of endogenous production of progesterone.

Clinical significance: The PRG level is related to corpus luteum, so we can use PRG as indicator of ovulation. How? If the level of PRG at luteal phase (21st d) is similar to that of follicular phase, or The summation of three consequent measures at the last seven days of cycle, is less than 15 ng/mL, indicates that the cycle is anovulatory cycle, which could be the cause of infertility.

Estrogen (E2) Functions: secondary sex characteristics of females. regulation of menstrual cycle, maintenance of pregnancy, Prevention of lactation during pregnancy, as it prevents prolactin action. Structurally, E2 consists of an 18C. In blood, E2 is strongly bound to SHBG and loosely to albumin, while only 2-3% is free.

Metabolism: E2 forms reversible redox system with oestrone, which is metabolized through two pathways; 2-hydroxylation pathway, with production of catecholestrogen and 16-hydroxylase pathway with formation of oestriol. Some pathological conditions, such as in hyperthyroidism, the hydroxylation pathway are increase. liver disease or hypothyroidism the reverse occurs.

Biosynthesis: produced by ovarian tissue which has active aromatase system that converts androgens to estrogen? Estrogen is inactivated in liver and excreted in urine. This explain the features of feminization in male patients with liver cirrhosis.

In menopausal women the main source of estrogen is from peripheral adrenal conversion of androstenedione to oestrone. The site for conversion is adipose tissue, Oestrone is almost always bound to albumin. Oestrone is using in diagnosis of post-menopausal bleeding and menstrual dysfunction especially in obese women.

During pregnancy the source of estrogen is the placenta, the main estrogen produced is oestriol. So that it is only used during pregnancy to evaluate the foeto-placental dysfunction. Estradiol is almost always secreted from ovaries, therefore is essential for checking of ovarian function and reserve with other hormones (LH, FSH, PRL, AMH) .

Disorders of the gonads: Primary ovarian failure: Hypergonadotropin Hypogonadism low oestrogen levels,stimulate secretion of high levels LH and FSH e.g. menopause and turner syndrome. Secondary ovarian failure: Hypogonadotropin Hypogonadism low levels of LH and FSH resulting in low levels of estrogen e.g. hypopituitarism. Both can result in amenorrhoea and infertility.

Q: How we can investigate ovarian reserve in order to introduce infertile couples to IVF program? In addition to age & ultrasonography (AFC), Five hormones are used which are LH, FSH , inhibin B , AMH and E2 (estradiol) blood collection occur at day 2 or 3 of cycle. If the levels of LH and FSH are low (mostly less than 6 mIU/L) and E2 level is high (mostly more than 85 ng/l). AMH can be measured regardless of cycle day and a level more than 1 microgram/ml is normal . the ovarian reserve is good (No ovarian failure and we can include them in IVF program).

Also alevel of AMH more than 5 mic/ml Q: What is the role of LH and FSH in in diagnosis of polycystic ovarian syndrome (PCOS)? A high LH/FSH ratio at day 2 or 3 of cycle is an indicator of presence of PCOS. Also alevel of AMH more than 5 mic/ml

Q: What other biochemical and pathophysiological changes that occur with polycystic ovarian syndrome (PCOS)? Aromatase activity is reduced in polycystic than in normal ovaries, w may explain the hyperandrogenism in this syndrome. Another characteristic feature of PCOS is insulin resistance ( compensatory hyperinsulinemia). Hyper-insulinemia results in increased ovarian androgen biosynthesis and decreased sex hormone–binding globulin (SHBG) synthesis from the liver, leading to increased bioavailability of free androgens. excess in ovarian androgen production causes anovulation.

(just idea) hyperinsulinemia may have a direct effect on hypothalamus and pituitary to increase serum LH concentrations and, indirectly, increased LH-dependent ovarian androgen biosynthesis, resulting in abnormal LH and FSH release and subsequent oligoamenorrhea.

Male Gonads

LH stimulates Leydig's cells of testes to secrete- testosterone. In males; LH stimulates Leydig's cells of testes to secrete- testosterone. It inhibits LH secretion by negative feedback inhibition, similar to ovarian hormone (E2) in females. Androgens: These are a group of 19 C steroids, required for differentiation of male genital tract and development of secondary male sex characteristics. They also influence muscle bulk, bone mass and sexual performance in males.

Hypothalamus- Pituitary- Gonadal Axis

Testosterone is converted to a more potent steroid called DHT by the 5-reductase, which is present in prostate, genital skin and seminal vesicles. Metabolism 78% testosterone is bonds to SHBG, 19% loosely bound to albumin and 3% of total is free, which is the active form. Most of these androgens are converted irreversibly to 17-ketsteroids which conjugate with glucoronic acid, excreted as water-soluble substances in urine.

The highest level of testosterone in males occurs in the morning and gradually decreases to 25% in evening. Slow and progressive decline occurs after 5th decade of life. In females, highest level is during puberty or 1 to 2 days at mid cycle.

Clinical disorders androgen (testosterone) deficiency two types depending on the tissue affected; primary or testicular disease (hypergonadotrophin hypogonadism) and secondary or hypothalamic or pituitary diseases (hypogonadotrophin hypogonadism). Whatever the type is the patient may present with delayed puberty or loss of previously established male characters such as hair distribution, potency and libido).

In testicular failure due to any cause e. g In testicular failure due to any cause e.g. Klinefelter's syndrome or testicular surgical removal, low level of testosterone, with stimulation of LH, so the blood levels of both LH & FSH will be higher than normal. Explain why the FSH level is also increased in patients with testosterone deficiency however its level is not controlled by it?

Answer/ FSH stimulate spermatogenesis and its level is not controlled by testosterone, but by another factor called inhibin, which is secreted from Sertoli's cells of testes. Sertoli's cells function depend on both FSH & testosterone, so low testosterone may result in decreased inhibin production by Sertoli cells which will stimulate high FSH production from pituitary gland.

Spermatogenesis defect: In hypothalamic or pituitary diseases, levels of LH and FSH are low, so level of testosterone is also low. This is secondary testicular failure (secondary endocrine disease). Spermatogenesis defect: Spermatogenesis (process of sperm formation) occurs in Sertoli's cells of testes through the action of FSH and testosterone.

FSH level [unlike LH] not controlled by testosterone but by special glycoprotein secreted from Sertoli's cells called inhibin. If there is low FSH or low testosterone (due to any disease) , this will result in oligospermia or azoospermia and of course infertility in males. Therefore, the indicators of defect in spermatogenesis are high levels of FSH (in blood), with very low level of inhibin.