Gonadotropin-releasing Hormone Release by Superfused Hypothalami in Response to Norepinephrine

Abstract

We have been studying the release of gonadotropin-releasing hormone (GnRH) from adult male rat medial basal hypothalamus (MBH) utilizing a continuous flow superfusion system. This model system allows for direct application of modifying substances into the superfusion chambers and for continuous collection of effluent for radioimmunoassay of GnRH levels. Gonadotropin-releasing hormone is rapidly released in response to specific chemical stimuli. As demonstrated by others, pulses of KCI or prostaglandin E₂ (PGE₂) result in sharp peaks of GnRH release followed by rapid return to baseline. Forty millimolar KCI increases (GnRH] 3- to 4-fold, consistent with a membrane-associated secretory process for GnRH release. A 50-μg bolus of PGE₂ results in a 2-fold rise in GnRH

Norepinephrine stimulates the release of GnRH in a log-linear dose-dependent manner in the range of 10⁻⁹ to 10⁻⁵ M norepinephrine (NE). At 10⁻¹¹ M, NE does not increase GnRH release above baseline, whereas at 10⁻⁹ M NE GnRH release is increased 2-fold. The α-receptor blocker phentolamine significantly inhibits the NE-induced rise in GnRH. Propranolol, a β-adrenergic receptor blocker, does not inhibit the GnRH response to NE.

This study demonstrates a direct, dose-dependent, α-mediated stimulatory effect of NE on GnRH release from superfused male rat MBH, and establishes the potential of this system for the investigation of the GnRH response to other aminergic agents and their extraneural modifiers, including steroid hormones.