Interaction between prolactin and catecholamines on hypothalamic GnRH release in vitro

Abstract

Brain catecholamines have been implicated in the regulation of gonadotrophin release. It has been recently reported that noradrenaline (NA), applied within the hypothalamic paraventricular nucleus, suppresses the pulsatile release of LH in the rat through a corticotrophin-releasing hormone (CRH)-dependent mechanism. Prolactin (PRL) is also able to suppress hypothalamic GnRH release following activation of the CRH-releasing neurone. Given that PRL stimulates the release of NA from hypothalamic explants and that NA stimulates the release of hypothalamic CRH, we hypothesized that this neurotransmitter may be involved in the intrahypothalamic neuroendocrine circuit mediating the inhibitory effects of PRL on GnRH release. To test this hypothesis, we evaluated the effects of PRL on GnRH release in the presence of alpha- or beta-adrenergic receptor antagonists using a static hypothalamic organ culture system which enabled us to evaluate immunoreactive GnRH (iGnRH) release from individually incubated, longitudinally halved hypothalami. As previously shown, PRL at a concentration of 100 nM inhibited basal iGnRH release by about 35%. Phentolamine, a non-selective alpha-adrenergic receptor antagonist, prazosin, an alpha 1-receptor antagonist, and yohimbine, an alpha 2-receptor antagonist, overcame the inhibitory effect of PRL on iGnRH release in a concentration-dependent fashion. In contrast, propranolol, a non-selective beta-adrenergic receptor antagonist, atenolol, a beta 1-receptor antagonist, and ICI-118,551, a beta 2-receptor antagonist, had no effect. None of these compounds had any effect on basal iGnRH release. These findings suggested that an alpha-adrenergic mechanism is involved in the suppressive effects of PRL on GnRH release. Since the activation of alpha-adrenergic receptors increases hypothalamic CRH release, we evaluated whether PRL stimulates CRH release via an alpha-adrenergic mechanism. PRL stimulated basal CRH release by about twofold and this effect was inhibited by phentolamine in a concentration-dependent fashion. In conclusion, alpha-, but not beta-, adrenergic receptors mediate the inhibitory effects of PRL on GnRH release in vitro. We speculate that, at least under these experimental conditions, PRL inhibits GnRH release through an alpha-adrenergic mechanism which activates the CRH-secreting neurone.

Increased hypothalamic expression of prolactin in lactation: involvement in behavioural and neuroendocrine stress responses

“…Further, the enhanced expression of the PRL gene in the hypothalamus during lactation (Fig. 5) suggests an action of PRL on corticotropin‐releasing hormone neurons (Kooy et al ., 1990), possibly mediated by adrenergic neurons (Calogero et al ., 1996). This hypothesis is supported by our recent demonstration of PRL release within the PVN of conscious rats under basal and stimulated conditions (Torner & Neumann, 2001).…”

In vivo release and gene upregulation of brain prolactin in response to physiological stimuli

“…The PRL released within the MPOA could act synergistically with PRL released within the PVN to modulate other neurotransmitter systems such that they inhibit corticotropin‐releasing hormone secretion and subsequent adrenocorticotropic hormone secretion from the pituitary. Previous studies have suggested similar actions of PRL on corticotropin‐releasing hormone neurons affecting the hypothalamo‐pituitary‐gonadal axis, presumably via adrenergic neurons (Calogero et al. , 1996).…”

Effect of LPS on Reproductive System at the Level of the Pituitary of Anestrous Ewes

“…Inhibitory effect of prolactin on the GnRH secretion may arise not only from the direct effect of prolactin on GnRH neurons, but most of all prolactin could affect GnRH release indirectly through the modulation of dopaminergic and CRH systems (Koike et al. 1991; Calogero et al. 1996).…”