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  • Title: Pulsatile control of reproduction.
    Journal: Lancet; 1984 Aug 18; 2(8399):382-3. PubMed ID: 6147459.
    Abstract:
    An aspect of the neuroendocrine regulation of reproduction to emerge in the past decade is the pulsatile nature of hormone secretion. The pulse generator is in the central nervous system -- in the medial basal region of the hypothalamus. It works by a synchronous firing of entire populations of endocrine neurons, which discharge a quantum of the decapeptide gonadotropin-releasing hormone (GnRH) into the portal blood capillaries which then carry it to the anterior pituitary gland. In man, episodic secretion of pituitary gonadotropins, especially luteinizing hormone (LH) is considered to imply a preceding pulsatile GnRH stimulus also, though this cannot be observed directly. This LH pattern is characterized by discrete bursts (pulses) separated by periods of little or no secretion. It is observalbe at all stages and states of reproductive life, being most evident at high secretion rates (e.g., at midcycle and after menopause). The pulse frequency is important and leads to the possibility of physiological and pharmacological control of pituitary-gonadal function by frequency modulation. Physiologically, pulses of LH secretion occur every 1-2 hours. The need for pulsatility in therapeutic GnRH stimulation of the pituitary also has been established following the early days of GnRH therapy when both constant and infrequent administration were found to be ineffective. Pulsatile GnRH therapy through portable pumps delivering small doses subcutaneously or intravenously every 1-2 hours has now been successfully applied to the treatment of anovulatory infertility, male hypogonadism, and the initiation of puberty. Supraphysiological GnRH stimulation, whether through increased frequency or amplitude or use of the "superactive" agonist analogues, produces a seemingly paradoxical inhibition of gonadotropin secretion. Although a postreceptor effect has been proposed, the mechanism appears to be a "down-regulation" of the GnRH receptors. Normally, the gaps between the physiological pulses allow time for receptor recycling or regeneration. This inhibitory effect has led to an expanding range of applications for the GnRH agonists in situations where a specific reduction or abolition of gonadotropin secretion is beneficial, including contraception (both male and female) and the management of endometriosis, precocious puberty, and sex hormone dependent cancers. For the gonads, too, pulsatile stimulation may be important. The pulses initially generated in the hypothalamus become blunter, but they can be detected in ovarian estradiol secretion in the follicular phase and progesterone secretion in the luteal phase. Although the pulsatile hormone production has its origin in the brain, the effects are seen throughout the reproductive system.
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