Selectivity of Melatonin Pituitary Inhibition for Luteinizing Hormone-Releasing Hormone

Abstract

The pineal indole melatonin suppresses the neonatal rat luteinizing hormone (LH) and follicle-stimulating hormone (FSH) responses to LH-releasing hormone (LHRH), as shown in previous studies from this laboratory. We show in this study that the melatonin inhibition is a selective effect and is not due to general inhibition of pituitary function. The effects of the indole on the responses to thyrotropin-releasing hormone (TRH) and somatostatin (SRIF) and on basal pituitary hormone secretion were examined with cells in culture. Neonatal rat anterior pituitary cells dissociated with collage-nase and hyaluronidase were cultured overnight and distributed to 35-mm dishes at the time of use. For examination of melatonin effects on the response to releasing hormones, the cells were incubated for 3 h in control medium or medium containing LHRH (10^–9-10^–6M), TRH (10^–10-10^–6M), or SRIF (10^–9-10^–6M), either alone or in the presence of melatonin (10^–8 or 10^–6M). For examination of basal hormone secretion, the cells were incubated for 1.5, 3, 6, 15, or 24 h in either medium alone or medium containing melatonin (10^–6M). Medium and cell lysate concentrations of LH, FSH, thyroid-stimulating hormone (TSH), prolactin (PRL) and growth hormone (GH) were determined by double antibody RIA. As previously, melatonin (10^–8M) significantly suppressed LH and FSH release by all concentrations of LHRH. This concentration of the indole produced maximal suppression of both LH and FSH responses to LHRH.By contrast, melatonin at a 100-fold greater concentration (10^–6M) had no effect on TRH stimulation of TSH or PRL release or on SRIF inhibition of GH release. Similarly, melatonin had no effect on basal release of TSH, PRL, or GH at the times examined. These findings show that melatonin inhibition of the gonadotroph response to LHRH is a selective effect.

Melatonin in Human Preovulatory Follicular Fluid*

“…Its mechanism and site of action are still uncertain. Most studies suggest that melatonin exerts its main effect on the pituitary or within the central nervous system, either by suppressing pituitary responses to GnRH (14,29) or by inhibiting pulsatile hypothalamic GnRH secretion (30). However, circulating melatonin could also have a direct effect on the gonads.…”

“…Prolonged darkness, which prolongs melatonin synthesis, suppresses gonadal function in several mammalian species (5-7). Recently, melatonin was reported to be involved in such human reproductive processes as puberty (8) and the menstrual cycle (9-11).It is generally thought that melatonin exerts its antigonadotropic effect mainly at the level of the brain and pituitary (12)(13)(14). However, exogenous melatonin was found to be concentrated in rat and cat ovaries (15), and specific melatonin receptors were reported (16) in hamster, rat, and human ovaries.…”

“…It is generally thought that melatonin exerts its antigonadotropic effect mainly at the level of the brain and pituitary (12)(13)(14). However, exogenous melatonin was found to be concentrated in rat and cat ovaries (15), and specific melatonin receptors were reported (16) in hamster, rat, and human ovaries.…”

Differential Effects of Short Photoperiod on 2-[¹²⁵l]lodomelatonin Binding in the Testis and Brain of Quail

“…In the rat, a high density of pituitary 2-[l25I]iodomeIatonin binding sites was reported in neonatal animals. In adult rats, however, pituitary 2-[l25I]iodomelatonin binding sites were drasti cally reduced suggesting that pineal melatonin action on the pituitary may be restricted to the neonatal period [10,13]. Conversely, a significant number of 2-[l25I]iodomelatonin binding sites were demonstrated in the ma ture chicken and quail testis and/or ovary [11,12].…”

Differential effects of melatonin on the stimulated release of LH from dispersed pituitary cells of the prepubertal female rat

“…The effect was observed in pituitary glands from female rats aged 5, 10 or 15 days, but not older rats. Further studies (Martin, McKellar & Klein, 1980) revealed a similar effect in vivo, and Martin & Sattler (1982) showed that the inhibitory effect of melatonin was selective in that the stimulated release of thyrotrophin and prolactin by thyrotrophin-releasing hormone or the inhibition of growth hormone (GH) by somatostatin was not affected by melatonin in their pituitary cell cultures. More recently, Lang, Aubert, Conne et al (1983) showed that suitably timed low-dose melatonin administration will inhibit or delay sexual maturation in male rats.…”