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Castration-Induced Modifications of GnRH-Elicited [Ca2+]i Signaling Patterns in Male Mouse Pituitary Gonadotrophs In Situ: Studies in the Acute Pituitary Slice Preparation1

ABSTRACT Gonadotropin-releasing hormone (GnRH) binds to pituitary gonadotroph receptors and initiates [Ca2+]i signals and gonadotropin secretion. Here, we recorded GnRH-induced Ca2+ signals in acute pituitary slices from both intact and castrated male mice 15 and 45 days after orchiectomy (GnX). Cells responding with “noncanonical” sequences of Ca2+ signaling to increasing GnRH concentrations ([GnRH]; oscillatory responses at a given [GnRH] and transient responses at both lower and higher concentrations) were augmented significantly in the castrated mice. Also, 15 days after GnX the number and size of gonadotrophs were augmented, confirming earlier anatomical studies. Hypertrophied gonadotrophs after 15 days after GnX tended to display GnRH-induced Ca2+ responses of greater amplitude. Furthermore, median effective dose (ED50) for GnRH decreased from 0.17 nM (control) to ∼0.07 nM after GnX, suggesting increased GnRH responsiveness of the gonadotroph population. The progression of Ca2+ response patterns reported in control male rat gonadotrophs (oscillations declining and spike-plateau responses dominating at increasing [GnRH]) was less conspicuous in mouse gonadotrophs in situ. Also, GnX-induced alterations in rat gonadotrophs (persistence of Ca2+ oscillations even at [GnRH] >100 nM) were not mirrored by mouse gonadotrophs in situ. Contrary to observations in intact and 15-day castrated mice, after 45 days of GnX the hump component diminished and oscillations were augmented with increasing [GnRH], but Ca2+ response patterns of gonadotrophs in situ remained virtually unchanged in response to [GnRH]s >1 nM, suggesting dose discrimination failure at high [GnRH]s. This study underscores the notion that GnRH responsiveness and the effects of testosterone deficiency may not be equal in pituitary gonadotrophs across species.