The Alpha-1-Adrenergic Neuronal System Is Involved in the Pulsatile Release of Luteinizing Hormone-Releasing Hormone in the Ovariectomized Female Rhesus Monkey

Abstract

It has been postulated that catecholamines are integral to the control of LHRH release. In the present study, the roles of adrenergic and dopaminergic receptors in the control of pulsatile LHRH release are examined. The effects of prazosin (an αi-antagonist), rauwolscine (an α₂-antagonist), propranolol (a β-antagonist), haloperidol (a dopamine antagonist), SCH23390 (a D₁ antagonist), and LY163502 (a D₂ agonist), on in vivo LHRH release in the stalk-median eminence were tested in ovariectomized female rhesus monkeys using push-pull perfusion. Prazosin caused a significant suppression of the LHRH release. This was primarily due to a significant suppression of LHRH pulse amplitude, but not pulse frequency, i.e. the interpulse interval was not affected by the administration of prazosin. In contrast to prazosin, none of the other adrenergic or dopaminergic drugs had significant effects on LHRH release. We conclude from these results that (1) the stimulatory effects of norepinephrine (NE) and/or epinephrine on pulsatile LHRH release are mediated by αi -adrenergic receptors but not α₂or β-adrenergic receptors, and (2) dopaminergic receptors do not appear to be involved in pulsatile LHRH release in ovariectomized rhesus monkeys.

Indirect assessment of pulsatile gonadotropin-releasing hormone release in agonadal prepubertal rhesus monkeys (Macaca mulatta)

“…In such studies, inter-GnRH-pulse intervals of approximately 1 h have been described for juvenile ovariectomized monkeys . In adult ovariectomized monkeys, direct and indirect assessment of GnRH pulse frequency has yielded comparable estimates of this parameter, namely approximately 1 pulse/h (Dierschke et al 1970, Wilson et al 1984, Gearing & Terasawa 1991. Since the present indirect analysis of GnRH pulse frequency in the prepubertal animal employed a pituitary with a responsiveness similar to that in the adult, the lack of congruency between the results obtained by the two methods in the prepubertal state must therefore be related to the smaller GnRH signal at this stage of development.…”

Estradiol Enhances Prostaglandin E2Receptor Gene Expression in Luteinizing Hormone-Releasing Hormone (LHRH) Neurons and Facilitates the LHRH Response to PGE2by Activating a Glia-to-Neuron Signaling Pathway

“…In earlier reports, we and others (Ojeda et al, 1982;Gearing and Terasawa, 1991) postulated that NE stimulates PGE 2 by binding to ␣ 1 -adrenergic receptors located on LHRH neurons and that, consequently, PGE 2 was an intracellular messenger acting within the LHRH neuron itself. There are, however, several findings indicating the need to revise this concept.…”

Expression of gonadotropin-releasing hormone receptors and autocrine regulation of neuropeptide release in immortalized hypothalamic neurons.

“…The receptor-mediated actions of GnRH on the neuronal network of GnRH cells (6,7), with decreases in the frequency and increases in the amplitude of GnRH pulses, lead to switching of the pattern of neuropeptide secretion from the basal pulsatile mode to one of episodic secretion and surge-like release as observed during the preovulatory period (34). Several other neuropeptides are known to modulate the activity of the GnRH pulse generator and may participate in the control of the preovulatory GnRH surge (8)(9)(10)(11)(12)(13)(14)(15)(16). There is also abundant evidence that estrogen promotes the development of the midcycle luteinizing hormone surge (35)(36)(37).…”

“…Recently, pulsatile neuropeptide secretion was found to be an intrinsic property of GnRH neuronal networks and to depend on voltage-sensitive Ca2+ influx for its maintenance (4-7). The activity of the GnRH pulse generator is influenced by several factors, including endothelin, N-methyl-D-aspartate, opiates, -aminobutyrate, and a-adrenergic input, as well as estrogens and androgens (8)(9)(10)(11)(12)(13)(14)(15)(16)). In addition, GnRH has been proposed to exert an inhibitory action on its own secretion (17-19); however, the mechanism and circuitry of such an ultrashort loop feedback effect have not yet been defined.…”