Physiology 5th Ed.


Gonadotropin Secretion Over the Lifetime

In both males and females, gonadal function is driven by the hypothalamic-pituitary axis, whose activity varies over the life span, as shown in Figure 10-2.


Figure 10–2 Gonadotropin secretion over the life span in males and females. FSH, Follicle-stimulating hormone; LH, luteinizing hormone.

Secretion of gonadotropin-releasing hormone (GnRH), the hypothalamic hormone, begins at gestational week 4, but its levels remain low until puberty. Secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), the anterior pituitary hormones, begins between gestational weeks 10 and 12. Like GnRH, the levels of FSH and LH remain low until puberty. During childhood, FSH levels are relatively higher than LH levels.

At puberty and throughout the reproductive years, the secretory pattern changes: Secretion of GnRH, FSH, and LH increases and becomes pulsatile. The relative levels of FSH and LH reverse, with LH levels becoming higher than FSH levels. In addition, in females, there is a 28-day cycle of gonadotropin secretion called the menstrual cycle.

Finally, in senescence, gonadotropin secretion rates increase further, with FSH levels becoming higher than LH levels, as they were in childhood.

Pulsatile Secretion of GnRH, FSH, and LH

The primary event at puberty is the initiation of pulsatile secretion of GnRH. This new pattern of GnRH secretion drives a parallel pulsatile secretion of FSH and LH by the anterior lobe of the pituitary. One of the earliest events of puberty is the appearance of large nocturnal pulses of LH during REM sleep. Another significant event early in puberty is an increased sensitivity of the GnRH receptor in the anterior pituitary. Thus, at puberty, GnRH up-regulates its own receptor in the anterior pituitary, and a given concentration of GnRH produces a greater stimulation of FSH and LH secretion. In addition, there is a shift in the relative secretion rates of the two anterior pituitary hormones; at puberty and throughout the reproductive period, LH levels are greater than FSH levels (compared with childhood and senescence, when FSH is greater than LH).

Pulsatile secretion of FSH and LH stimulates secretion of the gonadal steroid hormones, testosterone and estradiol. Increased circulating levels of the sex steroid hormones are then responsible for the appearance of the secondary sex characteristics at puberty.

The onset of the maturational process at puberty is genetically programmed, and familial patterns are evident. For example, the age at menarche (the onset of menses) is similar between mothers and daughters. The mechanisms underlying the onset of pulsatile GnRH secretion, however, remain a mystery. There may be gradual maturation of the hypothalamic neurons that synthesize and secrete GnRH. The central nervous system and nutritional status may alter the process; for example, extreme stress or caloric deprivation in girls delays the onset of puberty. It has been suggested that melatonin plays a role in the onset of puberty. Melatonin, secreted by the pineal gland, may be a natural inhibitor of GnRH release. Melatonin levels are highest during childhood and decline in adulthood, and this decline may release an inhibition of GnRH secretion. In support of a role for melatonin is the observation that removal of the pineal gland precipitates early puberty.

Characteristics of Puberty

As noted, the biologic events at puberty are set in motion by the onset of pulsatile activity in the hypothalamic–anterior pituitary axis. In turn, this pulsatile, or bursting, activity causes the testes and ovaries to secrete their respective sex hormones, testosterone and estrogen, that are responsible for the development of the secondary sex characteristics. Pulsatility of the hypothalamic-pituitary axis is required for normal reproductive function, as illustrated by the treatment of persons with delayed puberty caused by GnRH deficiency. If a GnRH analogue is administered in intermittent pulses to replicate the normal pulsatile secretory pattern, puberty is initiated and reproductive function is established. However, if a long-acting GnRH analogue is administered, puberty is not initiated. The events of puberty and their timing are illustrated in Figure 10-3.


Figure 10–3 Major events of puberty in males and females.

In boys, puberty is associated with activation of the hypothalamic-pituitary axis, Leydig cell proliferation in the testes, and increased synthesis and secretion of testosterone by the Leydig cells. There is growth of the testes, largely because of an increased number of seminiferous tubules. There is growth of the sex accessory organs such as the prostate. There is a pronounced linear growth spurt, and the epiphyses close when adult height is attained. As plasma levels of testosterone increase, facial, pubic, and axillary hair appears and there is growth of the penis, lowering of the voice, and initiation of spermatogenesis(spermarche).

In girls, puberty also is associated with the activation of the hypothalamic-pituitary axis, which drives the synthesis of estradiol by the ovaries. The first observable sign of puberty in girls is budding of the breasts, which is followed in approximately 2 years by menarche, the onset of menstrual cycles. The growth spurt and closure of the epiphyses typically begin and end earlier in girls than in boys. The appearance of pubic and axillary hair precedes menarche and is dependent on increased secretion of adrenal androgens, called adrenarche.