Fig. 2. Frequent blood sampling (every 10 min for 24 h) for luteinizing hormone (LH) in a normal man and a man with idiopathic hypogonadotropic hypogonadism (IHH). (A) Normal adult male pattern of gonadotropin-releasing hormone (GnRH) secretion with high amplitude LH pulsations (10 pulses in 24 h), normal serum testosterone levels, and normal testicular volume; (B) Apulsatile pattern of GnRH secretion in an IHH male as assessed by a complete absence of endogenous LH pulsations, low serum testosterone levels, and prepubertal sized testis.
events. During the neonatal window, the initial activation of the hypothalamic-pitu-itary-gonadal axis triggers an elevation of T to levels close to those of adult men. These high T levels are believed to direct the completion of the inguinoscrotal phase of testicular descent and the further growth of the phallus (15). Before the onset of puberty, there is a gradual threefold increase in testis size, as evidenced by postmortem studies in monkeys and childhood trauma victims. This increase is caused by a lengthening of the seminiferous tubules, resulting mainly from intense proliferation of Sertoli cells and, to a lesser degree, of immature germ cells (16,17). These events occur before Ser-toli cell maturation and the initiation of spermatogenesis. Two waves of postnatal Ser-toli cell proliferation occur, the first during infancy and the second at early puberty (16). Both coincide with discrete developmental windows of neuroendocrine activity (16,18,19). The cessation of Sertoli cell proliferation and initiation of Sertoli cell maturation occur during early puberty and result in the establishment of the blood-testis barrier, formation of a lumen, high-protein synthesis capacity, and the initiation of spermatogenesis (20,21). Ultimately, this final complement of mature Sertoli cells is the major determinant of testes size, seminiferous tubular development, and sperm counts (22), because each Sertoli cell supports a finite number of germ cells (23,24).
Thereafter, a dramatic increase in meiotic germ cells promotes the most significant increase in testis size that occurs during puberty. Germ cell development is highly organized and precisely timed and involves the interaction of groups of germ cells with Sertoli cells. Finally, improvement of spermatogenic efficiency leads to complete maturation of the seminiferous tubules (20,25). Although intratesticular T plays a central role in stimulating spermatogenesis, both directly and in concert with FSH, the increase in systemic T levels also induces adult males' secondary sexual characteristics. The specific role of FSH in adult males is not yet well established. However, based on the phenotype of the males with mutations in either the FSH-P or FSH receptor (FSH-R) (see Chapter 6), FSH is necessary to maintain both qualitative and quantitative normal spermatogenesis.
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