Neural signals that regulate GnRH neurones directly during the oestrous cycle
The oestrous/menstrual cycle results from an intricate orchestration of neurochemical and endocrine events acting at the central nervous system, anterior pituitary and ovary (Freeman, 1994; Hotchkiss and Knobil, 1994). GnRH neurones represent the final output pathway of the neural network that integrates a multitude of internal and environmental cues to regulate the secretion of LH and FSH from the anterior pituitary gland. Different patterns of pulsatile secretion of GnRH into the hypophyseal
... to the hypophyseal portal system, along with changes in the responsiveness of the pituitary gonadotrophs to GnRH, cause the changes in LH and FSH secretion observed over the oestrous cycle. The most marked of these changes is the massive outpouring of LH at mid-cycle, a critical event responsible for initiating ovulation. The ovary secretes oestradiol and progesterone, which feedback to the central nervous system and anterior pituitary to regulate the synthesis and patterns of release of GnRH and the gonadotrophins, as well as the responsiveness of the gonadotrophs to GnRH (Freeman, 1994; Hotchkiss and Knobil, 1994). During most periods of the oestrous cycle, oestradiol and progesterone restrain GnRH-mediated LH secretion through negative feedback. However, during prooestrus, these two steroid hormones, coupled with circadian input, exert positive feedback on GnRH neurones and the pituitary gonadotrophs to generate the preovulatory LH surge. Although recent data indicate that oestradiol may act directly on certain GnRH neurones through specific nuclear receptors, evidence in published studies has demonstrated that neurotransmission of afferent neuronal systems that are sensitive to oestradiol and progesterone is necessary to stimulate GnRH neurones to induce the mid-cycle LH surge (Kalra, 1993; Kordon et al., 1994). The purpose of this review is to detail the recent progress made toward deciphering the neurochemical signals involved in the control of cyclic GnRH secretion in the oestrous cycle of rats. Specifically, the current understanding of the functional significance of substances that communicate directly with GnRH neurones will be examined. Emphasis is placed on detailing the means by which oestradiol, neurotransmitters and neuropeptides interact and then communicate directly with GnRH neurones to drive reproductive cyclicity. This review focuses upon the female rat, and does not address the role of progesterone since its influence is entirely dependent upon pre-exposure to oestradiol.