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Progress in the field of neuroendocrinology continues at an astounding pace. Advances in technology and methodology have afforded us new insights into the interactions between complex neuronal circuitries and the balance of the endocrine system. These interactions are bidirectional; the regulation of endocrine secretions is controlled directly or indirectly by the nervous system and in turn the hormonal milieu can have profound effects on the function of the brain. From an endocrine perspective, advances in neuroendocrinology have occurred as a result of new insights into the actions and regulation of known hormones, the discovery of new actions and effects of known hormones, and the discovery of new hormones.The topics selected for this section encompass these divergent avenues of progress. Sally Radovick et al. review recent advances in our understanding of the regulation of gonadotropin-releasing hormone (GnRH). This hypothalamic factor stands at the crossroads of the central nervous system and the reproductive endocrine system and is critical for the integration of the well-being of an individual and his/her reproductive development and function. The periodicity and rhythmicity of the release of GnRH is critical for appropriate responses of the reproductive system and serves as an illustration of circadian as well as infradian and ultradian rhythms (pp. 153–159). Akwa and Baulieu review the roles of dehydroepiandrosterone sulfate (DHEAS) and dehydroepiandrosterone (DHEA) as neuroactive neurosteroids. These compounds have been traditionally considered to be products of the adrenal glands, serving largely as precursors for androgen synthesis. The discovery that DHEAS and DHEA can be synthesized in the nervous system has broadened our thinking about the functions and distributions of steroids and about the nature of neurotransmitters. Indeed, as Akwa and Baulieu review, we have learned that these steroids have autocrine/paracrine actions in the nervous system, influencing behavior, memory, and aging (pp. 160–167). Finally, Cyril Bowers reviews developments in the field of growth hormone releasing peptides (GHRP), in particular the recent isolation of the probable natural GHRP hormone, ghrelin. It is astonishing that, despite the many years of biochemical isolation and purification of hormones and the more recent applications of molecular cloning, we can continue to unearth novel hormones that prove to have physiological and clinical importance (pp. 168–174).The effects of environmental and metabolic cues on reproductive function have been observed and documented for many years and studies using animal models as well as human disease models have demonstrated that many of these effects occur at the level of GnRH dysregulation. As comprehensively reviewed here by Radovick et al., a variety of neurotransmitters are now known to converge to modulate GnRH production directly and indirectly. These neurotransmitters mediate the effects of immune challenges to reproductive function (corticotropin-releasing hormone and arginine vasopressin), nutritional and metabolic status (leptin), and season and exposure to daylight (melatonin). Recently, the molecular mechanisms that translate these environmental conditions into changes in GnRH production have begun to be elucidated. The advent of a variety of novel tools and techniques have helped to advance this field. The availability of estrogen receptor alpha null and progesterone receptor null mouse models have been invaluable to the study of the roles of gonadal steroids in the positive and negative feedback regulation of GnRH. The development of transformed cultured GnRH-expressing cell lines by Radovick and Mellon has led to new insights into factors that may play a role in GnRH neuronal migration, survival, and protection from apoptosis. Finally, the application of genetic approaches to the clinical study of patients with hypogonadotropic hypogonadism has led to an awareness of the heterogeneity of this patient population.

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