Neuroendocrine control processes. Pubertal onset and progression.

This discussion has outlined current concepts in neuroendocrinologic control of pubertal onset and progression. Central nervous system regulation of the arcuate nucleus (ventromedial hypothalamus) pulse generator that subsequently controls pituitary gonadotropin synthesis and secretion has been highlighted. Significant investigative issues that deserve assessment in the next several years include the following: 1. Systematic neuropharmacologic, electrophysiologic, and anatomic assessment of the hypothalamic arcuate nucleus. These assessments would include the use of recombinant DNA technology to probe cellular regulation of GnRH production. 2. Physiologically oriented examination of hypothalamic GnRH synthesis and secretion, along with function in the remaining reproductive endocrine system, during situations of nutritional impairment and excessive energy utilization and psychologic stress. 3. Further assessment of the neurophysiologic inhibition of GnRH production during childhood and the late prepubertal reactivation of the arcuate nucleus pulse generator. Roles of opioids, dopamine, other neurotransmitters, and metabolic signals remain to be clarified. 4. Exploration of regulators of hypothalamic, pituitary, and gonadal function when pulsatile GnRH administration has replaced the usual hypothalamic mechanisms. Pituitary-gonadal interactions may be independently assessed. 5. Assessment of pubertal growth, endocrine function, and neuropharmacologic control mechanisms in circumstances of chemical removal of pituitary gonadotrope function by GnRH agonists or antagonists. 6. Concordance and discordance of potency estimates of gonadotropins made by bioassay and immunoassay. The biologic basis for qualitative changes in bioassayable levels of LH and FSH, often related to carbohydrate content of the glycoprotein, may help to explain changes of gonadal function during the pubertal process. The potential for significant molecular heterogeneity of the gonadotropins is recognized and suggests substantial posttranslational changes of LH and FSH. 7. A cogent delineation of the hormonal, nutritional, and energy regulators of the pubertal growth spurt, though not discussed in this manuscript, remains to be accomplished. The relationship between pituitary gonadotropins and growth hormone, sex steroids, and the various peptide growth factors, especially the relationship between the growth factors and intragonadal steroidogenesis and germ-cell production, remain to be resolved. The importance of local production and action of peptide-growth factors in diverse tissues, skeletal and other, is being increasingly recognized.(ABSTRACT TRUNCATED AT 400 WORDS)