Gonadal Feedback Regulation of LHRH Release and Actions in the Rat

Abstract

It is now well established that the intermittent discharge of luteinizing hormone releasing hormone into the hypophyseal portal vasculature serves as the primary neural determinant of pulsatile LH secretion (1–7). The endocrine (nonneural) regulation of pulsatile LH secretion, by contrast, is dominated by the actions of gonadal steroid hormones operating in both negative (males and females) and positive (females) feedback modes. Both forms of gonadal feedback regulation appear to be mediated by alterations in the amount or pattern of pulsatile LHRH release, as well as by modulation of pituitary responsiveness to the decapeptide. Given the central importance of these feedback loops in the maintenance of reproductive viability, it is not surprising that much attention has been focused on the nature of the neural and endocrine mechanisms that mediate both types of hormonal feedback. In the work summarized below, we have used a variety of approaches to measure, manipulate, and mimic LHRH and LH release patterns, so that we might analyze and compare the mechanisms by which positive and negative feedback actions may be manifest. The concept is advanced that negative and positive feedback regulations at the hypothalamic level differ not only in sign, but also in the fundamental mechanisms by which LHRH neurons may ultimately mediate these processes. Specifically, a case is made for frequency and amplitude modulation as the primary bases for negative and positive feedback regulation, respectively.