Correspondence of Gonadotropin-Releasing Hormone and Luteinizing Hormone Secretion during Suckling in Postpartum Cows

The hypothalamus in the lower part of the brain contains neurons that produce a small peptide, gonadotropin- releasing hormone (GnRH, LHRH), that regulates luteinizing hormone (LH) secretion by the anterior pituitary gland. Important functions of LH include induction of ovulation in preovulatory follicles during estrus and the luteinization of granulosa cells lining those collapsed follicles to form corpora lutea that produce progesterone during the luteal phase of the estrous cycle or during pregnancy. The production of progesterone by the corpus luteum conveys a negative feed-back action at the central nervous system (CNS) for further episodic secretion of GnRH and in turn, LH secretion. Gonadal removal (i.e., ovariectomy) allows a greater amount of LH secretion to occur during a prolonged period. The objectives of this study were to characterize the pattern of GnRH secretion in the cerebrospinal fluid (CSF) of the bovine third ventricle region of the hypothalamus, determine its correspondence with the tonic and surge release of LH in ovariectomized cows, and examine the dynamics of GnRH pulse release activity in response to known modulators of LH release (suckling, neuropeptide-Y [NPY]). In ovariectomized cows, both tonic release patterns and estradiol-induced surges of GnRH and LH were highly correlated. A 500-microgram dose of NPY caused an immediate cessation of LH pulses and decreased plasma concentrations of LH for at least 4 hours. This corresponded with a decrease in both GnRH pulse amplitude and frequency. In anestrous cows, GnRH pulse frequency did not change before and 48 to 54 hours after weaning on day 18 postpartum, but GnRH concentration and amplitudes of GnRH pulses increased in association with weaning and heightened secretion of LH. It is clear that high-frequency, highamplitude pulses of LH are accompanied by similar patterns of GnRH in CSF of adult cattle. Yet strong inhibitors of LH pulsatility, putatively acting at the level of the central nervous system (i.e., suckling) or at both the central nervous system and pituitary (NPY) levels, produced periods of discordance between GnRH and LH pulses.

Effects of Novel Growth Hormone Secretagogues on Growth Hormone Secretion in Farm Animals

The requirement for growth hormone (GH) secretion by the anterior pituitary gland in beef calves is demonstrated by a complete lack of long bone-growth and muscle accretion after hypophysectomy (surgical removal of the pituitary gland). When the connecting link (hypophyseal stalk) to the basal region (hypothalamus) of the brain is surgically severed, long bone growth and body weight gain are greatly limited compared with sham-operated controls. This limited growth results from obliteration of episodic GH secretion and reduced basal blood concentration of the hormone compared with sham-operated controls. Thus, the hypophyseal stalk-transected (HST) calf provides an appropriate model to determine mechanisms by which hypothalamic neuropeptides from the brain regulate GH secretion, and thereby growth in the young calf. Neuropeptides have been isolated and characterized in bovine hypothalamus that stimulate GH secretion (GH-releasing hormone [GHRH]) or factor [GHRF] and inhibit GH secretion (GH release-inhibiting hormone [GHRIH] or somatostatin [SRIH]). A dose of .067 micrograms of GHRF per kilogram of body weight injected intravenously in HST calves abruptly increased plasma GH concentration to 55 nanograms per milliliter from the control period mean of 5 nanograms per milliliter. HST calves then were infused intravenously with .033 and .067 microgram somatostatin per kilogram of body weight, during which a pulse injection of .067 microgram of GHRF was administered. GH increase was limited to 9 and 5 micrograms per kilogram body weight during the .033- and .067 microgram SRIH infusions after GHRF; no GH rebound was observed after the SRIH was discontinued. GHRF from humans contains 40 to 44 amino acids. Rat hypothalamic GHRF analogs containing 29 to 32 amino acids elicited dose-dependent GH peak release in these HST calves. In 1977, Bowers and Monomy isolated novel GH releasing peptides consisting of only six amino acids; they caused GH release by isolated pituitary cells in culture and acute GH release when administered intravenously. We recently have utilized a novel nonpeptidyl GH secretagogue of low molecular weight in the pig to determine its mechanisms of action within the central nervous system.