Gonadotropin-releasing hormone pulses: regulators of gonadotropin synthesis and ovulatory cycles.

The data reviewed present evidence that the pattern of GnRH secretion is an important factor in the regulation of gonadotropin subunit gene expression, gonadotropin synthesis, and secretion. The information on regulation of mRNA expression by GnRH pulses should be considered with some caution, as the experiments were performed in male rats and may not accurately reflect events in female primates or humans. However, an overall pattern emerges which suggests that common factors may be involved in all mammalian species. If current evidence is correct, and only a single gonadotropin-releasing hormone exists, then mechanisms to differentially regulate the three gonadotropin genes may involve changes in GnRH secretion. Alterations in GnRH pulse frequency and amplitude are recognized by the pituitary gonadotrope cell and could be the mechanism used to effect differential expression of the gonadotropin subunit genes. Differential regulation of subunit gene expression would be expected to be critically important in the establishment of pubertal maturation, and subsequently in the maintenance of ovulatory cycles in women. Our hypotheses, proposing a major role of pulsatile GnRH secretion in the regulation of human reproduction, are summarized in schematic form in Fig. 14 for men and Fig. 15 for women. In utero and during the first few months of life, GnRH is secreted at a relatively fast frequency (approximately 1 pulse/hour). During the first year, GnRH secretion is inhibited and both the amplitude and apparent frequency of pulsatile release is markedly reduced. The mechanisms involved in inhibiting GnRH release remain unclear in humans. Similarly, the mechanisms involved in the disinhibition of GnRH secretion, which first occurs during sleep at the initiation of puberty, are unclear, but in humans do not appear to involve opiates. In males, the increased frequency and amplitude of GnRH secretion favor LH synthesis and release, which in turn stimulates testosterone secretion (Fig. 14). Testosterone acts at the hypothalamus, perhaps through opioid mechanisms, to inhibit GnRH pulse frequency and to maintain a regular pattern of pulses occurring approximately every 90-110 min in adult males. In females, the mechanisms involving alterations in the patterns of GnRH secretion to regulate reproduction appear more complex. This may reflect the need to differentially synthesize and secrete FSH and LH at different times during reproductive cycles to allow orderly follicular maturation and ovulation. As shown in Fig. 15, we hypothesize that the events during the first decade of life and through the initiation of nocturnal GnRH secretion at puberty are similar in both sexes.(ABSTRACT TRUNCATED AT 400 WORDS)