Hypothalamic alpha adrenergic receptors and the regulation of LHRH release

The neurotransmitter system regulating the release of luteinizing hormone releasing hormone (LHRH) has been actively investigated since the classic 1947 work of Sawyer. The literature indicates that LHRH release is primarily under the control of the $\alpha$ adrenergic system. The $\alpha$ adrenergic receptor subtype mediating LHRH release has not been established however. Also, most investigators have used changes in plasma luteinizing hormone to infer changes in hypothalamic LHRH release, rather than directly examining LHRH release. The purpose of this work was to directly examine the release of hypothalamic LHRH and determine if $\alpha\sb1$ or $\alpha\sb2$ receptors mediates changes in its release. Initially, this thesis demonstrates that the in vitro pulsatile administration of 10$\sp{-5}$M of the $\alpha\sb1$ adrenergic agonist methoxamine (MTX) stimulates LHRH release from superfused female rat mediobasal hypothalami. This is a specific effect, blocked by the $\alpha\sb1$ antagonist prazosin. This data was the first to demonstrate that the specific activation of hypothalamic $\alpha\sb1$ adrenoceptors sharply stimulates the release of LHRH. This effect occurred in hypothalami from proestrus and ovariectomized rats with or without estrogen.To establish that $\alpha\sb1$ stimulation of LHRH release also occurs in vivo, the push-pull cannula (PPC) technique was used. Via the PPC, LHRH release showed moderate pulsatility during the initial baseline period. Immediately following infusion of 10$\sp{-4}$M MTX there was a robust, significant, increase in LHRH release. This indicates that the activation of rat MBH $\alpha\sb1$ adrenoceptors stimulates LHRH release in vivo also, and that this stimulatory $\alpha\sb1$ effect is an underlying physiological mechanism. In a second PPC experiment, infusion of 10$\sp{-4}$M prazosin decreased LHRH release, indicating that basal LHRH release is also modulated by $\alpha\sb1$ receptors. The $\alpha\sb2$ adrenergic agonist $\alpha$-methyl-norepinephrine and antagonist yohimbine had no effect upon in vitro LHRH release. Last, median eminence LHRH terminals from in vitro superfused and in vivo PPC hypothalami were immunocytochemically stained. Superfusion and PPC had no apparent effect upon LHRH terminals.U of I OnlyETDs are only available to UIUC Users without author permissio