Melatonin Inhibition of the <i>in vivo</i> Pituitary Response to Luteinizing Hormone-Releasing Hormone in the Neonatal Rat

Abstract

The effects of melatonin on the in vivo pituitary LH response to LH-releasing hormone (LHRH) were examined in neonatal male and female rats, in 35- to 44-day-old male rats, and in 35- to 44-day-old male animals which had been either pinealectomized or maintained in constant light for at least 3 weeks before use. Animals were given saline or melatonin (1–100 μg/rat) followed within 30 sec by saline or LHRH (10–1,000 ng/rat) at separate subcutaneous sites. Blood was collected following decapitation either without prior injection or 15, 30, 45, or 60 min afterwards. Serum LH concentrations were determined by double antibody radioimmunoassay. In neonatal male and female rats, melatonin (1 μg) significantly (p < 0.01) suppressed by approximately 65% serum LH at 15 min after LHRH. Suppression was maintained for at least 60 min, a finding which indicates that melatonin blocks rather than delays the response to LHRH. By contrast, in normal, pinealectomized, and constant light older male rats, melatonin (100 μg) had no detectable effect on either the magnitude or the time course of LH release by LHRH. These data extend our previous in vitro findings by demonstrating that melatonin is a potent inhibitor of the in vivo pituitary response to LHRH in neonatal rats but not in older animals. Neither pinealectomy nor constant light, both of which are assumed to reduce pineal melatonin production, for at least 3 weeks before use restores neonatal pituitary responsiveness to the pineal indole in the older animals.

International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, Classification, and Pharmacology of G Protein-Coupled Melatonin Receptors

“…In immortalized GnRH-releasing cells, activation of endogenous MT 1 and MT 2 receptors decreased the expression of GnRH mRNA in a 24-h cyclical manner, which was blocked by luzindole (Roy et al, 2001). In the neonatal rat pituitary gland, melatonin inhibits GnRH-induced LH release, cAMP and cGMP accumulation, and increases in intracellular Ca 2ϩ through activation of a pertussis toxinsensitive GPCR (Martin et al, 1980;Vanecek and Vollrath, 1990;Vanecek and Klein, 1995). The mechanism(s) by which melatonin modulates pituitary gonadotropin secretion involves activation of MT 1 melatonin receptors (Johnston et al, 2003a,b); however, participation of MT 2 receptors (Balík et al, 2004) cannot be excluded.…”

Selectivity of Melatonin Pituitary Inhibition for Luteinizing Hormone-Releasing Hormone

“…Mela tonin exerts this effect both in intact animals [14,17] and in pituitary cultures [13,15,16], thus clearly defining the neo natal rat pituitary gland as a target tissue of this pineal hor- mone. Melatonin acts rapidly on the pituitary gland to suppress gonadotropin release within minutes after simul taneous administration with LHRH.…”

Melatonin Does Not Affect Luteinizing Hormone-Releasing Hormone Binding to Neonatal Rat Anterior Pituitary Membranes

“…Melatonin (1 pAi) suppressed the LH response to 10 pAi D-Ala by 51%, and the peptide antagonist at 10 and 100 nAi similarly inhibited release by 33 and 84%, respectively. These data clearly show that while melatonin and the LHRH peptide antagonist both suppress stimulated LH release by gonadotrophs in cul ture, melatonin does not antagonize the binding of D-Ala to the LHRH receptor.The pineal indole melatonin inhibits the luteinizing hor mone-releasing hormone (LHRH)-stimulated release of lu teinizing hormone (LH) and follicle-stimulating hormone by the neonatal rat anterior pituitary gland as shown in previous studies from this laboratory [10,13,15). This effect is evident both in intact animals and in cultured pituitary cells at physiological concentrations of the pineal indole.…”