Review of Medical Physiology - William F. Ganong 2002

Endocrine System, Metabolism, and Reproduction
Sexual Differentiation and Development
Sexual Differentiation and Development - Puberty

As noted above, enhanced testosterone secretion in the male fetus occurs even before birth (Fig. 23-9). During the neonatal period, a further rise is observed, The Significance of which remains unclear, after which Leydig Cell activity declines. Subsequently, in all mammals, there follows a quiescent period during which the Gonads of both sexes are inactive until they are stimulated by pituitary gonadotropins for the final maturation of the Reproductive System. This period of final maturation is known as adolescence, or Puberty; during this time, the endocrine and gametogenic Functions of the gonads first attain a state that enables reproduction. In girls, the first event is thelarche (breast development), followed by pubarche (appearance of pubic and axillary Hair), and finally menarche (the first Menstrual cycle). Typically, the initial cycles are anovulatory, with regular ovulation becoming established approximately a year later.

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Fig. 23-9. Plasma testosterone concentration in males as a function of age.

Unlike adults, children exhibit a slight increase in gonadotropin secretion from birth until the onset of puberty, indicating that gonadotropin release is independent of Sex Hormones. In children aged 7 to 10 years, a gradual rise in estrogen and androgen secretion precedes the more rapid growth spurt of early adolescence (Fig. 23-10).

The age at the onset of puberty varies. In Europe and North America, it has been decreasing by one to three months per decade for over 175 years. In Eastern Europe (including Ukraine), the age of puberty in recent years typically ranges from 8 to 13 years in girls and from 9 to 14 years in boys.

Another phenomenon observed in humans during puberty is the increased adrenal secretion of androgens (Fig. 23-11), a process known as adrenarche. This occurs between the ages of 8 and 10 years in girls and 10 and 12 years in boys. Peak DHEA levels are reached around the age of 25 in women, occurring slightly later than in men, and gradually decline after age 60. The adrenal secretion of androgens during adrenarche increases without any Changes in the secretion of cortisol or ACTH. This may be due to an alteration in the adrenal enzyme system, which channels more pregnenolone into the androgen pathway (see Chapter 20). Alternatively, evidence suggests that this process is driven by an increase in the secretion of an adrenal androgen-stimulating hormone (AASH) from the Pituitary Gland.

Fig. 23-10. Changes in plasma hormone concentrations during puberty in boys (top) and girls (bottom). Tanner stage 1 represents the prepubertal period in both sexes. In boys, stage 2 corresponds to initial testicular enlargement, Stage 3 to penile elongation, stage 4 to growth of the Penis and Development of the glans, and stage 5 to adult genitalia. In girls, stage 2 corresponds to breast budding, stage 3 to elevation and enlargement of the breasts, stage 4 to PROJECTION OF THE areolae, and stage 5 to adult breast configuration (modified and reproduced with permission from Grumbach MM: Onset of puberty. In: Puberty: Biologic and Psychosocial Components. Berenberg SR [editor]. H.E. Stenfert Kroese B.V., 1975).

Control of Puberty

In children, the gonads can be stimulated by pituitary gonadotropins, and the Hypothalamus contains GnRH (see Chapter 14). However, gonadotropins are not secreted during this prepubertal period. In immature monkeys, normal menstrual cycles can be induced by the pulsatile administration of GnRH, and these cycles persist as long as the hormone administration is maintained.

Notably, GnRH is secreted in a pulsatile manner during fetal life. Consequently, it is evident that from birth until puberty, a neural mechanism operates to suppress the normal pulsatile release of GnRH. The exact Nature of the mechanism inhibiting the GnRH pulse generator remains poorly understood.

Fig. 23-11. Serum dehydroepiandrosterone sulfate (DHEAS) levels as a function of age. The solid line represents mean values, and the dashed lines represent ±1.96 standard deviations (reproduced with permission from Smith MR et al: A radioimmunoassay for the estimation of serum dehydroepiandrosterone sulfate in normal and pathological sera. Clin Chim Acta 1975; 65:5).

Influence of Leptin

It was long believed that a critical body mass must be attained for puberty to begin. For example, young female athletes who experience significant weight loss often develop Amenorrhea. Similarly, girls with anorexia nervosa experience cessation of menses, which resume once they normalize their nutritional intake and regain weight, thereby returning to a pubertal state. It has now been discovered that leptin—a hormone predominantly produced by adipocytes (see Chapter 14)—may serve as the metabolic link between body mass and the onset of puberty. Obese ob/ob mice, which are incapable of producing leptin, are infertile, but their reproductive capacity is restored following leptin administration. Leptin Treatment also induces precocious puberty in immature female mice. The precise role of leptin in the general Regulation of human puberty remains to be fully elucidated.