Intraventricular injection of agents that enhance cyclic adenosine monophosphate formation leads to inhibition of proestrous luteinizing hormone surge in rats

Abstract

Taleisnik S, Haymal B, Caligaris L. Intraventricular injection of agents that enhance cyclic adenosine monophosphate formation leads to inhibition of proestrous luteinizing hormone surge in rats. Acta Endocrinol 1993:129:273-8. The effect of increasing hypothalamic levels of 3\m=' \,5\m=' \-cyclicadenosine monophosphate (cAMP) on the preovulatory surge of luteinizing hormone (LH) and ovulation was studied in cycling rats. Animals bearing chronically implanted guiding cannulae into the third ventricle were injected with agents known to enhance the cellular levels of cAMP. Hourly blood samples from the unanesthetized, unrestrained rats were obtained between 11.00 and 1 7.00 h through a plastic cannula inserted into the jugular vein. Intraventricular injections of serotonin (7.5 mg/ml; 2 \g=m\l ) in the morning of proestrous blocked the preovulatory surge of LH and ovulation. This effect was assigned to an increased neuronal level of cAMP because it was prevented by a serum anti-cAMP. Third-ventricle injections of 2 \ g=m\ l of forskolin (0.5 mmol/l), guanosine 5\m='\-0-(3-thiotriphosphate)(2 mmol/l) or dibutyryl-cAMP (1 mmol/l) at 11.00 h on the day of proestrus mimicked the inhibitory effect of serotonin on the proestrous release of LH. It is suggested that serotonin inhibits LH surge by acting directly on LH-releasing hormone neurons and/or on neurons that provide inputs to these neurons involving cAMP as a second messenger. Neurons releasing \g=g\-aminobutyricacid (GABA) may serve as interneurons sensitive to serotonin, as well as to cAMP, inasmuch as the inhibitory effect of forskolin on the release of LH was partially blocked by the GABA antagonists, picrotoxin and bicuculline.Regulation of gonadotropin secretion depends directly on the secretion of gonadotropin-releasing hormone (GnRH). The neurons that elaborate and secrete this hormone form a continuum from the telencephalic diagonal band of Broca and the diencephalic areas of the periventricular, preoptic and anterior hypothalamic areas. These neurons constitute a final common path¬ way of which the most prominent projection is to the median eminence (1). Inputs to the GnRH neurons play a fundamental role in controlling the secretion of the products of these neurons. There is evidence for synaptic associations between GnRH neurons and nerve endings containing dopamine /Miydroxylase (2), tyrosine hydroxylase (2-4), y-aminobutyric acid decarboxylase (2, 5), neurotensin and substance P (6, 7), serotonin (8), opioids (9, 10) and neuropeptide Y (11). In addition, a variety of neurotransmitters have been demonstrated to influence the secretion of luteinizing hormone (LH) (12).The generation of cyclic adenosine 3',5'-monophosphate (cAMP) is an obligatory step for the action of many neurotransmitters after their binding to specific recep¬ tors on the surface of the target cells. The accumulation of cAMP in GnRH neurons may therefore be a possible process in the action of neurotransmitters affecting LH secretion.The aim of this study was to explore whether changes...