Hypotheses on Control of the Onset of Puberty

In 1931, Hohlweg presented a so-called "gonadostat" theory of puberty, which was based on the concept of a changing sensitivity of the gonadotropin-regulating system to the negative feedback effect of gonadal steroids (20). This theory was further developed by Grumbach and colleagues (21). Hohlweg and Junkmann observed that

Feedback High

Decreasing sensitivity

Adult type

GnRH

Decreasing sensitivity

Adult type

GnRH

Testosterone Levels Puberty

LH/FSH

Onset of Puberty i

Prepuberty

Adulthood

Prepuberty

Onset of Puberty

Adulthood

Fig. 3. The "gonadostat" hypothesis for puberty, i.e., a developmental change in the sensitivity of the gonadotropin-releasing hormone (GnRH) system in the regulation of gonadotropin secretion. During prepuberty, sensitivity to the negative feedback actions of gonadal steroids is highest, resulting in a low release of GnRH and gonadotropins. Initiation of puberty is secondary to a decrease in sensitivity to gonadal steroid feedback inhibition, resulting in increased GnRH and gonadotropin release, until a new equilibrium level is reached in adulthood. (Modified from ref. 21.)

in castrated immature rats, small doses of steroid hormones prevented pituitary hypersecretion, whereas larger steroid doses were needed in adult rats (22). Similarly in the human, pituitary gonadotropin secretion is sensitive to the suppressive effect of sex steroids, because small doses of estrogen are able to suppress gonadotropin levels (21). Thus, according to this concept, the onset of puberty results from a decreasing sensitivity at the hypothalamic-pituitary level to the suppressive effect of sex steroids; consequently, gonadotropin secretion increases, and, in turn, there is an increase in gonadal steroid production (see Fig. 3). Testosterone infusion experiments in boys and men have shown a change in the mechanism of negative feedback with maturation. In boys, testosterone suppresses hypothalamic GnRH secretion, manifested by a decrease in LH pulse frequency but not amplitude, but the hypothalamus becomes resistant to testosterone negative feedback with puberty (23-25). Thus, according to the gonadostat theory, at the time of puberty, gonadal steroid feedback inhibition of gonadotropin secretion reaches a new equilibrium at a higher setpoint.

In the 1980s, however, it was found, that agonadal subjects had a pattern of changes in gonadotropin concentrations that was similar to that of healthy subjects through infancy and childhood, a finding that contradicted the "gonadostat" hypothesis. Therefore, in the 1980s, an alternative theory, called the "intrinsic restraint concept," was

Onset Puberty Factors

Fig. 4. Central nervous system (CNS) restraint hypothesis of puberty. Factors involved in the regulation of gonadotropin-releasing hormone (GnRH) secretion are listed. According to this idea, GnRH secretion is quiescent in childhood because of early neuronal growth, resulting in a restraint of GnRH release. Stimulating factors overcome this restraint and initiate GnRH release again at the onset of puberty.

Fig. 4. Central nervous system (CNS) restraint hypothesis of puberty. Factors involved in the regulation of gonadotropin-releasing hormone (GnRH) secretion are listed. According to this idea, GnRH secretion is quiescent in childhood because of early neuronal growth, resulting in a restraint of GnRH release. Stimulating factors overcome this restraint and initiate GnRH release again at the onset of puberty.

proposed (see Fig. 4). According to this concept, in addition to sex steroid-mediated negative feedback, a central inhibitory system restrains GnRH release and maintains the prepubertal phase. At the onset of puberty, the intrinsic CNS restraint is inhibited or is dominated by a stimulatory system (26). During the last decades, considerable evidence has been gathered to support this intrinsic restraint hypothesis (vide infra).

Yet a third hypothesis, called the "de-synchrony" theory, has been presented to explain the onset of puberty. This theory is based on a finding that GnRH concentrations in the hypothalamus of primates during prepuberty are comparable to those in the adult animals. Therefore, the lack of GnRH stimulation of the pituitary in prepuberty would result from the desynchronization of GnRH-secreting neurons (27).

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Responses

  • LEIGH CRAWFORD
    What overcomes gnrh inhibition at puberty?
    8 years ago
  • silvana
    What is gonadostat theory?
    2 years ago
  • selassie awate
    What is the gonadostat hypothesis?
    1 year ago

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