The Onset of Puberty Depends on Maturation of the Hypothalamic GnRH Pulse Generator

The onset of puberty depends on a sequence of matura-tional processes that begin during fetal life. The hypothal-amic-pituitary-gonadal axis undergoes a prolonged and multiphasic activation-inactivation process. By midgesta-tion, LH and FSH levels in fetal blood are elevated, reaching near adult values. Experimental evidence suggests that the hypothalamic GnRH pulse generator is operative at this time, and gonadotropins are released in a pulsatile manner. The levels of FSH are lower in males than in females, probably because of suppression by fetal testosterone at midges-tation. As the levels of placental steroids increase, they exert negative feedback on GnRH release, lowering LH and FSH to very low levels toward the end of gestation.

After birth, the newborn is deprived of maternal and pla-cental steroids. The reduction in steroidal negative feedback stimulates gonadotropin secretion, which stimulates the gonads, resulting in transient increases in serum testosterone in male infants and estradiol in females. FSH levels in females are usually higher than those in males. At approximately 3 months of age, the levels of both gonadotropins and gonadal steroids are in the low-normal adult range. Circulating gonadotropins decline to low levels by 6 to 7 months in males and 1 to 2 years in females and remain suppressed until the onset of puberty.

Throughout childhood, the gonads are quiescent and plasma steroid levels are low. Gonadotropin release is also suppressed. The prepubertal restraint of gonadotropin secretion is explained by two mechanisms, both of which affect the hypothalamic GnRH pulse generator. One is a sex steroid-dependent mechanism that renders the pulse generator extremely sensitive to negative feedback by steroids. The other is an intrinsic central nervous system (CNS) inhibition of the GnRH pulse generator. Together, they suppress the amplitude, and probably the frequency, of GnRH pulses, resulting in diminished secretion of LH, FSH, and gonadal steroids. Throughout this period of quiescence, the pituitary and the gonads can respond to exogenous GnRH and gonadotropins, but at a relatively low sensitivity.

The hypothalamic-pituitary axis becomes reactivated during the late prepubertal period. This response involves a decrease in hypothalamic sensitivity to sex steroids and a reduction in the effectiveness of intrinsic CNS inhibition over the GnRH pulse generator. The mechanisms underlying these changes are unclear but might involve endogenous opioids. As a result of disinhibition, the frequency and amplitude of GnRH pulses increase. Initially, pulsatility is most prominent at night, entrained by deep sleep,- later it becomes established throughout the 24-hour period. GnRH acts on the gonadotrophs of the anterior pituitary as a self-primer. It increases the number of GnRH receptors (up-regulation) and augments the synthesis, storage, and secretion of the gonadotropins. The increased responsiveness of FSH to GnRH in females occurs earlier than that of LH, accounting for a higher FSH/LH ratio at the onset of puberty than during late puberty and adulthood. A reversal of the ratio is seen again after menopause.

The increased pulsatile GnRH release initiates a cascade of events. The sensitivity of gonadotrophs to GnRH is increased, the secretion of LH and FSH is augmented, the go-nads become more responsive to the gonadotropins, and the secretion of gonadal hormones is stimulated. The rising circulating levels of gonadal steroids induce progressive development of the secondary sex characteristics and establish an adult pattern of negative feedback on the hypothal-amic-pituitary axis. Activation of the positive-feedback mechanism in females and the capacity to exhibit an estrogen-induced LH surge is a late event, expressed in midpu-berty to late puberty.

The onset of puberty in humans begins at age 10 to 11. Lasting 3 to 5 years, the process involves the development of secondary sex characteristics, a growth spurt, and the ac-


Breast bud begins

Pubic hair begins

Peak height spurt ^


Menarche Pubic hair adult Breast adult

Genital development begins Pubic hair begins


Peak height spurt

Genitalia adult Spermatogenesis^^^^^^^^^^

begins Pubic hair adult

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  • Betty
    Which gonadotropin stimulates the gonads to release testosterone in males?
    8 years ago

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