Gonadotropin-Releasing Hormone Secretion into Third-Ventricle Cerebrospinal Fluid of Cattle: Correspondence with the Tonic and Surge Release of Luteinizing Hormone and Its Tonic Inhibition by Suckling and Neuropeptide Y1

Abstract

Objectives of the current studies were to characterize the pattern of GnRH secretion in the cerebrospinal fluid of the bovine third ventricle, determine its correspondence with the tonic and surge release of LH in ovariectomized cows, and examine the dynamics of GnRH pulse generator activity in response to known modulators of LH release (suckling; neuropeptide Y [NPY]). In ovariectomized cows, both tonic release patterns and estradiol-induced surges of GnRH and LH were highly correlated (0.95; p < 0.01). Collectively, LH pulses at the baseline began coincident with (84%) or within one sampling point after (100%) the onset of a GnRH pulse, and all estradiol-induced LH surges were accompanied by corresponding surges of GnRH. A 500- microg dose of NPY caused immediate cessation of LH pulses and lowered (p < 0.001) plasma concentrations of LH for at least 4 h. This corresponded with declines (p < 0.05) in both GnRH pulse amplitude and frequency, but GnRH pulses were completely inhibited for only 1.5-3 h. In intact, anestrous cows, GnRH pulse frequency did not differ before and 48-54 h after weaning on Day 18 postpartum, but concentrations of GnRH (p < 0.05) and amplitudes of GnRH pulses (4 of 7 cows) increased in association with weaning and heightened secretion of LH. We conclude that the study of GnRH secretory dynamics in third-ventricle CSF provides a reasonable approach for examining the activity and regulation of the hypothalamic pulse generator in adult cattle. However, data generated using this approach must be interpreted in their broadest context. Although strong neurally mediated inhibitors of LH pulsatility (suckling; NPY) had robust effects on one or more GnRH secretory characteristics in CSF, only high doses of NPY briefly abolished GnRH pulses. This implies that the GnRH signal received at the hypophyseal portal vessels under these conditions may differ quantitatively or qualitatively from those in CSF, and theoretically would be undetectable or below a biologically effective threshold when LH pulses are absent.

Metabolic changes in early lactation and impaired reproductive performance in dairy cows

“…An in vivo study in cows showed that injection of NPY into the third cerebroventricle of ovariectomized cows, caused a decrease in amplitude of tonic LH secretion [94]. Another study of the same group revealed that NPY affected LH pulsatility in a dose-dependent manner, accompanied by changes in the concentration of GnRH in cerebrospinal fluid (CSF) [41].…”

The timing of puberty (oocyte quality and management)

“…From these portal veins, pituitary capillaries emerge and the GnRH is released in the intercellular space and reaches anterior pituitary cells. GnRH concentration in the portal veins varies between 4-100pg/ml (Caraty et al, 1982;Clarke and Cummins, 1982;Levine et al, 1982;Irvine and Alexander, 1987;Gazal et al, 1998), which gives a very small amount of GnRH for the small blood volume considered. Thus, the amount of GnRH that passes in the general circulation is very small; the concentration is well below the detection threshold of known hormonal assays.…”

“…Due to its small peptidic structure, circulating endopeptidases degrades rapidly the GnRH. Therefore to assess the GnRH secretion, blood should be punctured from pituitary portal vessels or from canulae inserted in the third ventricle (Gazal et al, 1998) and this can only be performed in large animals and requires invasive surgical procedures (Clarke and Cummins, 1982;Levine et al, 1982). An alternative is to follow LH secretion since it has been clearly demonstrated that a GnRH pulse precedes every LH pulse (Clarke and Cummins, 1982;Caraty et al, 1989).…”

Controle sobre GnRH durante o anestro pós-parto em bovinos

“…Esse peptídeo possui um padrão elevado de expressão no hipotálamo e na hipófise anterior de bovinos, sendo encontrado no corpo celular e em terminações nervosas de diversas áreas do cérebro, principalmente naquelas relacionadas com a regulação do consumo alimentar e o balanço energético (THOMAS et al, 1999). A administração central de NPY em ratos induz hiperfagia (STANLEY et al, 1986) e, em bovinos, inibe a liberação de GnRH e LH sem alterar os níveis plasmáticos de FSH (GAZAL et al, 1998). Além disso, a administração central de altas concentrações de NPY em ovelhas bloqueia completamente o pico pré-ovulatório de GnRH (ESTRADA et al, 2003).…”

“…No entanto, apesar da leptina ser capaz de reduzir a síntese e secreção de NPY (SAHU, 1998), ela não é capaz de atenuar os efeitos sobre a liberação do LH, quando esse neurotransmissor é injetado diretamente no SNC de vacas ovariectomizadas (GARCIA et al, 2004), sugerindo que, em bovinos, a leptina controla apenas as ações pré-secretórias do NPY. Ainda, parece que o NPY é capaz de controlar a liberação do LH na hipófise bovina, pois, após a infusão desse peptídeo diretamente no terceiro ventrículo hipotalâmico, a liberação do LH permaneceu totalmente bloqueada, mesmo após a pulsatilidade do GnRH estar restabelecida (GAZAL et al, 1998). Além de uma regulação na síntese de GnRH, foi demonstrado em camundongos que a leptina altera o potencial de resposta dos gonadotrofos frente ao estímulo do GnRH, através de um aumento da expressão de canais de Ca ++ (AVELINO-CRUZ et al, 2009).…”