DISORDERS OF SEX-STEROIDS

Development of gonads and external genitals is a complex interplay of various hormones, secreted from pituitary (gonadotropins), adrenals (androgens) and gonads themselves, together termed as sex-steroids.

Androgens: DHEAS (Dehydroepiandrosterone sulfate) is the predominant adrenal androgen in circulation, derived from adrenals directly or converted from peripheral sulfation of another adrenal androgen-DHEA. DHEAS levels are low in childhood but begin to rise before other hormonal changes at puberty to promote growth as well as secondary sexual characteristics, e.g. pubic/axillary hairs.

Testicular hormones: Testosterone is the main hormonal product of testis, secreted by Leydig cells from 8-12 weeks of gestation onwards and responsible for initial virilization of fetus. After initial virilization, testosterone level drop and remain low till onset of puberty when it increases again to cause testicular and penile growth, typical body odor and voice changes. Within target cells, some testosterone is converted into other derivatives, e.g. dihydrotestosterone and estradiol.

Other important testicular hormones include Mulle- rian-inhibiting substance (MIS) that causes involution of fetal mullerian ducts, inhibin-B and Follistatin that inhibit pituitary FSH secretions, and many other growth factors.

Ovarian hormones: Estrogens (estradiol, estrone and estriol) and progesterone are predominant hormones of ovary, though also produced by adrenals as well as testis. These hormones are critical for menstruation and development of breasts, as well as to exert a negative feedback on pituitary gonadotropins.

Other important ovarian hormones include inhibins, activins (diamers of inhibin, to promote FSH secretion) and many other growth factors.

Gonadotropins from pituitary, i.e. LH and FSH, are critical for onset of puberty as well as ovogenesis and menstrual changes in females.

Clinically, disorders of sex steroids may present at birth with ambiguous genitalia or later as delayed/pre- cocious puberty, gynecomastia, amenorrhea/sterility, etc. discussed in this chapter.

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