Mediation of the short-loop negative feedback of luteinizing hormone (LH) on LH-releasing hormone release by melatonin-induced inhibition of LH release from the pars tuberalis.

Abstract

The pineal hormone melatonin is thought to mediate the effects of the pineal gland on seasonal reproduction by altering the release of gonadotropins. The mechanism by which melatonin controls gonadotropin secretion has been ob- This concentration of melatonin also significantly reduced the release of LH into the medium. The increased release of LIIRH induced by melatonin (10 FM) was completely blocked by the addition of LH (50 ng/ml), which by itself had no sigicant effect on LHRH release. Rat LH antiserum (final dilution, 1:1800) significantly elevated LHRH output, whereas normal rabbit serum at a similar dilution had no effect. Finally, LHRH Melatonin, the pineal hormone, responds to seasonal changes in photoperiod to influence reproductive rhythms in seasonal breeders; however, the mechanism by which melatonin brings about its diverse effects is unknown (1). The development of a high-affinity high-specific-activity ligand, 2-[1251]iodomelatonin, has allowed the identification of melatonin-binding sites within the brain. The highest concentration of melatonin receptors occurs in the pars tuberalis of mammals (2-4), and it may be that this part of the vertebrate pituitary gland is not the nonfunctional lobe it was thought to be. The cells of this structure have many of the ultrastructural characteristics considered necessary for endocrine secretion (5). Furthermore, seasonal fluctuations in its cytological features, seemingly in concert with reproductive cycles, may represent the morphological expression of seasonal changes in its endocrine function (6). Luteinizing hormone (LH)-containing cells in the pars tuberalis of rats were first demonstrated through immunocytochemistry by Baker et al. (7), and it is noteworthy that the distribution of these cells corresponds to the distribution of terminals of the LH-releasing hormone (LHRH) neurons in the overlying median eminence. When the median eminencepars tuberalis was incubated in vitro in the presence of medium with a high potassium concentration, there was release of LH into the medium; LH release could also be stimulated by addition of LHRH (8). Although there is some evidence of LH in hypothalamic neurons, it appears that the largest amount of LH in the median eminence-pars tuberalis complex actually occurs in the gonadotrope-like cells in the pars tuberalis (21).The concept of short-loop feedback by which pituitary hormones inhibit their own release (9-11) is well established. The short-loop feedback of LH has been thought to be mediated either by LH neurons within the hypothalamus (11) or by retrograde flow of blood in the hypophyseal portal vessels that transport high concentrations of LH to the median eminence (12). We do not believe that either of these is the major mechanism for the LH negative short-loop feedback. Rather, we hypothesize that LH is released from the gonadotropes of the pars tuberalis and diffuses into the median eminence where it suppresses the release of LHRH from the terminals of the LHRH neurons either by a direct action or by...

Gonadotrophin-releasing hormone drives melatonin receptor down-regulation in the developing pituitary gland

“…Overall, MT 1 mRNA expression in this region was Ϸ4-fold higher in hpg mice, and liquid emulsion autoradiography showed a strong increase in expression around the PT-PD interface. Because gonadotrophs are present throughout this region (17,(38)(39)(40), these data are consistent with the hypothesis that GnRH down-regulates pituitary MT 1 expression in vivo. Based on this result, we suggest that melatonin receptor expression is a feature of a quiescent phase in the development of the hypothalamo-pituitary-gonadal axis, after the gonadotrophic phenotype has become established, but before the GnRH system is in place.…”

“…The maintained expression of MT 1 in the PT of wild-type animals is probably largely attributable the presence of a population of PT-specific thyrotroph cells in this region that are insensitive to both GnRH and thyrotropin-releasing hormone (17,34,35); indeed, although Klosen and colleagues found LH␤ positive cells in the rat PT, they were unable to detect LH␤ coexpression with MT 1 (17). Although explant experiments suggest that a small population of gonadotroph cells may remain melatonin-sensitive within the PT in adults (38,41), the receptor subtype responsible for this phenomenon has not been defined.…”

Advanced Prostate Cancer Is Associated with a Decrease in Serum Luteinizing Hormone

“…data]. Indications for an androgen–independent secretion of basal LH came also from in vitro experiments [23], from the lack of diurnal variations of LH in spite of such alterations with respect to T [24], and from variations of LH and T in serum induced by different treatments that were independent of each other to a considerable extent [25, 26]. …”

What is the role of melatonin within the anterior pituitary?

“…Two studies, one in the rat (Nakazawa et al 1991) and one in the sheep (Skinner & Robinson 1997), have reported that gonadotrophinreleasing hormone (GnRH)-induced LH release from PT explants is melatonin sensitive (albeit at supraphysiological concentrations of the hormone). The significance of this is unclear; it is unlikely that these cells significantly influence peripheral circulating TSH or gonadotrophin titres, but the possibility that these cells act locally -e.g.…”