Suppression of Progesterone-Induced Gonadotropin Surge by Adrenergic Agonists in Estrogen-Primed Ovariectomized Rats

Abstract

An involvement of catecholamines in the preovulatory gonadotropin surge has been proposed for many years. Specifically, an α-adrenergic mechanism has been implicated in the stimulation of ovulation and LH release. On the other hand, little is known regarding the possible role of adrenergic neurotransmission once a gonadotropin surge has been initiated. In this study, drugs which affect adrenergic receptors were administered centrally to estrogen-primed ovariectomized rats and the effects on serum concentrations of LH and FSH induced by treatment with progesterone at 08.00 h were examined. As expected, the progesterone treatment caused a significant (p < 0.05) increase in blood LH and FSH levels by 14.00 and 15.00 h, respectively, when compared with those seen at 13.00 h. In control rats that received isotonic saline intraventricularly at 15.00–16.00 h, both LH and FSH levels continued to rise linearly and reached peak levels by 17.00 and 18.00 h. By contrast, intraventricular infusion of norepinephrine at 16.00 h caused a significant decrease (p<0.05) in LH levels when compared with the saline-infused control groups. Moreover, rats that received intraventricular infusion of phenylephrine (an α₁-adrenergic agonist) at 15.00 h failed to show a significant increase in LH and FSH levels until 19.00 h; this inhibitory effect was mimicked by a relatively more specific α₁-adrenergic agonist, methoxamine. Consistent with our previous findings, animals which received intraventricular isoproterenol (a specific β-adrenergic agonist) at 15.00 h also responded with suppressed serum LH levels at 16.00–19.00 h when compared with controls. Thus, in addition to the well-known stimulatory role of NE and α-adrenergic agonists for the onset of the LH/FSH surge, these rather unexpected data suggest that α₁-adrenergic neurotransmitters may have a dual and paradoxical role and actually attenuate LH and FSH release (even in a steroid-primed environment) once a gonadotropin surge has been initiated.

Oestrogen Modulation of Excitatory Al Noradrenergic Input to Rat Medial Preoptic Gamma Aminobutyric Acid Neurones Demonstrated by Microdialysis

“…Infusion of NA directly into the medial preoptic area (MPOA) [ I] or third ventricle [2,3], and electrical stimulation of the ascending noradrenergic tracts [4] have all been shown to inhibit pulsatile LH secretion, predominantly through a reduction in LH pulse frequency. Studies by Bergen and Leung [5,6] have shown similar effects during the LH surge and demonstrated, as for the inhibition of pulsatile release [3], that a-adrenergic mechanisms are involved. However, nor adrenaline administered into the third ventricle prior to the oes trogen-progesterone-induced LH surge evokes increases in plasma LH levels [2,3].…”

Electrical Stimulation of Ventral versus Dorsal Mesencephalic Tegmental Areas in the Conscious Rat: Effects on Luteinizing Hormone Release

“…It would thus ap pear that epinephrine, but not NE, may be essential for the preovulatory gonadotropin surge [7], Indeed, it has been reported that perfusion of the third ventricle with NE ac tually suppresses the LH secretion response to stimulation of the medial preoptic area [8]. This is particularly interes ting in view of our recent finding that infusion of NE or ai-adrenergic agonists during an ongoing LH follicle-sti mulating hormone surge suppresses gonadotropin release, which further questions an obligatory role of NE for the occurrence of the gonadotropin surge [2],…”

Activation of the CNS Noradrenergic System May Inhibit as well as Facilitate Pituitary Luteinizing Hormone Release

“…Phenoxybenzamine would suppress the facilitatory component and permit the inhibitory component to be evident. In addition, NE reverses the rise in LH and FSH release induced by the injection of progesterone in ovariectomized, estrogen-primed rats [2],…”