Hormonal regulation of female reproduction.

Reproduction is an event that requires the coordination of peripheral organs with the nervous system to ensure that the internal and external environments are optimal for successful procreation of the species. This is accomplished by the hypothalamic-pituitary-gonadal axis that coordinates reproductive behavior with ovulation. The primary signal from the central nervous system is gonadotropin-releasing hormone (GnRH), which modulates the activity of anterior pituitary gonadotropes regulating follicle stimulating hormone (FSH) and luteinizing hormone (LH) release. As ovarian follicles develop they release estradiol, which negatively regulates further release of GnRH and FSH. As estradiol concentrations peak they trigger the surge release of GnRH, which leads to LH release inducing ovulation. Release of GnRH within the central nervous system helps modulate reproductive behaviors providing a node at which control of reproduction is regulated. To address these issues, this review focuses on several critical questions. How is the HPG axis regulated in species with different reproductive strategies? What internal and external conditions modulate the synthesis and release of GnRH? How does GnRH modulate reproductive behavior within the hypothalamus? How does disease shift the activity of the HPG axis?

Gonadotrophin-inhibitory hormone: a multifunctional neuropeptide.

Gonadotrophin-inhibitory hormone (GnIH) was discovered 8 years ago in birds. Its identification raised the possibility that gonadotrophin-releasing hormone (GnRH) is not the sole hypothalamic neuropeptide that directly influences pituitary gonadotrophin release. Initial studies on GnIH focused on the avian anterior pituitary as comprising the only physiological target of GnIH. There are now several lines of evidence indicating that GnIH directly inhibits pituitary gonadotrophin synthesis and release in birds and mammals. Histological studies on projections from hypothalamic GnIH neurones subsequently implied direct actions of GnIH within the brain and in the periphery. In addition to actions on the pars distalis via the median eminence, GnIH axons and terminals are present in multiple brain areas in birds, and the GnIH receptor is expressed on GnRH-I and -II neurones. Furthermore, we have demonstrated the presence of GnIH and its receptor in avian and mammalian gonads. Thus, GnIH can act directly at multiple levels: within the brain, on the pituitary and in the gonads. In sum, our data indicate that GnIH and its related peptides are important modulators of reproductive function at the level of the GnRH neurone, the gonadotroph and the gonads. Here, we provide an overview of the known levels of GnIH action in birds and mammals. In addition, environmental and physiological factors that are involved in GnIH regulation are reviewed.

Gonadotropin-inhibitory peptide in song sparrows (Melospiza melodia) in different reproductive conditions, and in house sparrows (Passer domesticus) relative to chicken-gonadotropin-releasing hormone.

Gonadotropin-releasing hormone (GnRH) regulates reproduction in all vertebrates. Until recently, an antagonistic neuropeptide for gonadotropin was unknown. The discovery of an RFamide peptide in quail that inhibits gonadotropin release in vitro raised the possibility of direct hypothalamic inhibition of gonadotropin release. This peptide has now been named gonadotropin-inhibitory hormone (GnIH). We investigated GnIH presence in the hypothalamus of two seasonally breeding songbird species, house sparrows (Passer domesticus) and song sparrows (Melospiza melodia). Using immunocytochemistry (ICC), GnIH-containing neurones were localized in both species in the paraventricular nucleus, with GnIH-containing fibres visible in multiple brain locations, including the median eminence and brainstem. Double-label ICC with light microscopy and fluorescent ICC with confocal microscopy indicate a high probability of colocalization of GnIH with GnRH neurones and fibres within the avian brain. It is plausible that GnIH could be acting at the level of the hypothalamus to regulate gonadotropin release as well as at the pituitary gland. In a photoperiod manipulation experiment, GnIH-containing neurones were larger in birds at the termination of the breeding season than at other times, consistent with a role for this neuropeptide in the regulation of seasonal breeding. We have yet to elucidate the dynamics of GnIH synthesis and release at different times of year, but the data imply temporal regulation of this peptide. In summary, GnIH has the potential to regulate gonadotropin release at more than one level, and its distribution is suggestive of multiple regulatory functions in the central nervous system.

Seasonal growth of song control nuclei precedes seasonal reproductive development in wild adult song sparrows.

In seasonally breeding adult songbirds, the brain regions that control song undergo dramatic seasonal morphological changes. During late winter and early spring, increasing day length triggers an increase in circulating testosterone that ultimately causes several song nuclei to grow in volume. The timing of this growth relative to the seasonal development of the reproductive system is not known. This question was investigated in two populations of wild song sparrows (Melospiza melodia morphna). Both populations live at the same latitude (46 degrees N), but breed at different altitudes. One population resides on the Pacific coast in Washington, and the other resides in the foothills of the Cascade Mountains. Both populations experienced the same photoperiodic conditions, but the timing of seasonal reproductive development differed between populations. Coastal birds initiated gonadal recrudescence approximately 2 weeks earlier than montane birds. Despite this temporal difference in reproductive development, there were no differences between these groups in the seasonal growth of two song control nuclei, HVc and RA. During late February, both groups had low circulatory levels of testosterone (mean for coastal birds was 1.01 +/- 0.37 ng/ml; mean for montane birds was 1.41 +/- 0.26 ng/ml) and fully recrudesced song nuclei (for example, mean HVc volume in coastal birds was 1.77 +/- 0.08 mm(3); mean HVc volume in montane birds was 1.76 +/- 0.09). Also at this time, both populations were in the earliest stages of seasonal reproductive development as judged by the degree of gonadal recrudescence (mean gonad volume was less than 10% of typical breeding size in both populations). It is concluded that seasonal song system growth is completed before seasonal reproductive development in response to submaximal levels of circulating testosterone.