Effect of Melatonin on the Luteinizing Hormone Release Induced by Clomiphene and Luteinizing Hormone-Releasing Hormone

Abstract

Much experimental evidence indicates that the pineal gland is involved in the regulation of reproductive function (1). This effect appears to be mediated, at least partially, by melatonin (2). It is well known that melatonin has a definite inhibitory influence on reproductive function (3,4). For instance, it has been demonstrated that the injection of melatonin into the third ventricle is followed by a decrease in the luteinizing hormone (LH) and follicle-stimulating hormone (FSH) plasmatic concentrations (4, 5 ) .Luteinizing hormone-releasing hormone (LH-RH) and clomiphene citrate are known to stimulate the release of LH in the rat. LH-RH stimulates the synthesis and release of LH at the anterior pituitary level (6), whereas there is evidence that clomiphene exerts its principal effect on the hypothalamus (7,8).The aim of the present study was to obtain information on the site or mechanism by which melatonin modifies the reproductive function. This was performed by studying the effect of the pineal principle on the LH release in response to LH-RH and clomiphene.Material and Methods. Adult male rats, from the strain of the Institute of Physiology of the Buenos Aires Medical School maintained in cycles of 14 hr of light and 10 hr of darkness and fed Purina laboratory chow ad libitum, were used for all experiments. Experiment 1. The effect of melatonin and clomiphene on LH secretion were studied in the following groups of rats: (i) con-] Supported by Grants from Consejo Nacional de Investigaciones Cientificas y TCcnicas and from Quimica Argentia, Buenos Aires, Argentina.Established Investigator, Consejo Nacional de Investigaciones Cientificas y TCcnicas, Buenos Aires, Argentina.trol; (ii) treated with clomiphene citrate (0.01 mg/100 g of body weight/day im, for 6 days); (iii) treated with melatonin (1 mg/day sc, dissolved in ethanol l o % , for 6 days); and (iv) treated with clomiphene and melatonin (the drugs were simultaneously administered with the same regimens and doses as described for groups 2 and 3). Controls received only the vehicles.Twenty-four hours after the last injection, the animals were killed by decapitation, blood samples were taken from the trunk for the LH assay, and the seminal vesicles and ventral prostate weights were recorded. Blood samples were allowed to clot at 4" and centrifuged, and the serum was separated and kept frozen until it was assayed. The concentration of LH in serum from individual rats was assayed in duplicate by means of the double-antibody radioimmunoassay as described by Niswender et al. (9). The results were expressed in terms of nanograms of NIAMD-RAT-LH-RP-l/ml of serum. The statistical analysis of the data, planned in the design of the experiment, consisted of the comparison of each experimental group vs control by means of Student's t test.Experiment 2. In this series the effect of pretreatment with melatonin on the LH release after LH-RH administration was studied. Rats were treated with 1 mg of melatonin sc (dissolved in 10% ethanol) for 6 days. Control rats were i...

Melatonin enhances guanylate cyclase activity in a variety of tissues

“…One criticism of this study is that the half life of melatonin is only 11 min (17) and these effects were seen 3 h later. Also, in contrast to the above study subcutaneous injections of melatonin for 6 days into rats did not prevent the pituitary response to LHRH (18). In addition, Kamberi et al (19) have reported that infusion of melatonin into hypophysial portal vessels of rats did not effect the level of LH in the plasma.…”

“…In addition, Kamberi et al (19) have reported that infusion of melatonin into hypophysial portal vessels of rats did not effect the level of LH in the plasma. One possible explanation for the negative findings of the infusion (19) and subcutaneous injection studies (18) was the low level of basal LH secretion in these studies which makes an inhibitory effect difficult to discern. The present investigation demonstrates that melatonin does have a direct effect on at least one enzyme system in the anterior pituitary.…”

Effect of the Serotoninergic System on Luteinizing Hormone Secretion in Prepubertal Female Rats

“…We have no adequate explanation of this finding, but it could be considered that around 20-to 26-day-old rats take place important events related to the hypothalamic control of go nadotropin secretion (the maturation of the positive feed back of ovarian steroids, for instance), that are probably connected with modifications in the effect of the different neurotransmitters on these pituitary hormones. In this re spect, it is interesting to note that changes in the effect of melatonin on LH-RH in prepubertal and adult rats has been described and it has been proposed that this modifica tion is involved in the maturation of the reproductive sys tem [10,13].…”

Role of the pineal gland in the regulation of prostatic androgen receptors in pubertal and mature rats

“…Melatonin, the gland's predominant hormone, has been primarily designated for this effect [24,25,28,32]. In the male rat melatonin has been found to decrease the secretion ofgonadotropins [6,13,17,21] and to modify the synthesis [22], metabolism [7,14], and activity [1,4] of gonadal androgens.…”