The male reproductive system regulates sex differentiation, virilization, and the hormonal changes that accompany puberty, ultimately leading to spermatogenesis and fertility. Under the control of the pituitary hormones—luteinizing hormone (LH) and follicle-stimulating hormone (FSH)—the Leydig cells of the testes produce testosterone and germ cells are nurtured by Sertoli cells to divide, differentiate, and mature into sperm. During embryonic development, testosterone and dihydrotestosterone (DHT) induce the wolffian duct and virilization of the external genitalia. During puberty, testosterone promotes somatic growth and the development of secondary sex characteristics. In adults, testosterone is necessary for spermatogenesis, stimulation of libido, normal sexual function, and maintenance of muscle and bone mass. This chapter focuses on the physiology of the testes and disorders associated with decreased androgen production, which may be caused by gonadotropin deficiency or primary testis dysfunction. A variety of testosterone formulations now allow more physiologic androgen replacement. Infertility occurs in ∼5% of men and is increasingly amenable to treatment by hormone replacement or by using sperm transfer techniques. For further discussion of sexual dysfunction, disorders of the prostate, and testicular cancer, see Chaps. 48, 95, and 96, respectively.


The fetal testis develops from the undifferentiated gonad after expression of a genetic cascade that is initiated by the SRY (sex-related gene on the Y chromosome) (Chap. 349). SRY induces differentiation of Sertoli cells, which surround germ cells and, together with peritubular myoid cells, form testis cords that later develop into seminiferous tubules. Fetal Leydig cells and endothelial cells migrate into the gonad from the adjacent mesonephros but also may arise from interstitial cells that reside between testis cords. Leydig cells produce testosterone, which supports the growth and differentiation of wolffian duct structures that develop into the epididymis, vas deferens, and seminal vesicles. Testosterone is also converted to DHT (see below), which induces formation of the prostate and the external male genitalia, including the penis, urethra, and scrotum. Testicular descent through the inguinal canal is controlled in part by Leydig cell production of insulin-like factor 3 (INSL3), which acts via a receptor termed LGR8 (leucine-rich repeat-containing G protein–coupled receptor 8, also known as GREAT: G protein–coupled receptor affecting testis descent). Sertoli cells produce müllerian inhibiting substance (MIS), which causes regression of the müllerian structures, including the fallopian tube, uterus, and upper segment of the vagina.


Although puberty commonly refers to the maturation of the reproductive axis and the development of secondary sex characteristics, it involves a coordinated response of multiple hormonal systems that include the adrenal gland and the growth hormone (GH) axis (Fig. 346-1). The development of secondary sex characteristics is initiated by adrenarche, which usually occurs between 6 and 8 years of age when the adrenal gland begins to produce greater amounts of androgens from the zona reticularis, the principal site of dehydroepiandrosterone (DHEA) production. The sex maturation process is greatly accelerated by the activation of the ...

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