Effect of Growth Retardation on Pituitary Luteinizing Hormone and Hypothalamic Neuropeptide Y in Ovariectomized Sheep

Abstract

The possible role of neuropeptide Y (NPY) in mediating the relationship between pituitary LH secretion and growth retardation due to restricted feeding was examined in ovariectomized (OVX) prepubertal ewe lambs. One specific objective examined whether there was an inverse relationship between concentrations of NPY in four diencephalic brain regions and pituitary LH secretion in ewe lambs 29-30 weeks old which had been growth retarded since 8 weeks and OVX at 24 weeks. Through dietary restriction, body weight was held constant at 20.7 ± 0.5 kg in 13 growth-retarded ewes as compared with 48.0 ± 0.6 kg for 5 age-matched control ewes at 29-30 weeks of age. Episodic LH was quantified at 10-min intervals for 190 min/day on 3 of the 8 days immediately before euthanasia. Serum LH averaged 6.5 ± 0.6 ng/ml in control ewes with a mean pulse frequency of 1.0 ± 0.1 pulses/h. Serum LH in growth-retarded ewes was much less episodic (0.2 ± 0.05 pulses/h) and averaged only 1.2 ± 0.2 ng/ml. All ewes were euthanized during week 30, and the following brain regions were dissected: basal forebrain, preoptic area, median eminence and remainder of hypothalamus. Following extraction, NPY concentrations (pg/mg of original tissue) were quantified by radioimmunoassay. In each brain region, NPY concentrations were greater (p < 0.05) in 6 growth-retarded ewes than in 5 control ewes (median eminence: 5.2 vs. 0.6; remainder of hypothalamus: 3.3 vs. 0.8; preoptic area: 3.1 vs. 0.8, and basal forebrain: 2.2 vs. 1.2). A secondary objective examined whether the LH and NPY parameters were rapidly altered by transient changes in feed consumption. Therefore, a subgroup of 7 growth-retarded ewes was given access to increased feed during the last week of the experiment (denoted as refed growth-retarded), but feed consumption and weight gain were highly variable as only 1 ewe maintained her initially increased feed consumption for the entire 7 days. Secretion of LH as reflected in mean concentrations (2.1 ± 0.5 ng/ml) and pulse frequency (0.4 ± 0.1 pulses/h) was slightly increased (p < 0.05) in refed ewes. However, NPY concentrations (median eminence: 6.6; remainder of hypothalamus: 3.6; preoptic area: 3.6, and basal forebrain: 2.5) in the 7 refed growth-retarded ewes were similar to those of the 6 growth-retarded ewes which were not refed. Among individual refed growth-retarded ewes, there was no clear relationship among weight gain/feed consumption and hypothalamic NPY. In summary, steroid-independent suppression of LH secretion in chronically growth-retarded ewes was inversely related to elevated levels of NPY in median eminence and other diencephalic regions. Increased food availability forpnly 7 days reversed only slightly the suppression of LH and did not affect the elevated levels of hypothalamic NPY. Except for these divergent changes in refed ewes, the main results of this study are consistent with the hypothesis that increased neural production of NPY contributed to suppression of LH release in growth-retarded OVX ewes.

Increased Galanin and Neuropeptide-Y Immunoreactivity within the Hypothalamus of Ovariectomised Ewes following a Prolonged Period of Reduced Body Weight Is Associated with Changes in Plasma Growth Hormone but Not Gonadotropin Levels

“…PVN and ARC most probably reflects increased NPY transport to these regions, pre sumably arising from increased NPY synthesis in the ARC. Using radio-immunoassay, Ober and Malven [55] evaluated NPY concentrations in the feed-restricted ewe lamb and found elevated peptide concentrations in the POA, MBH and anterior hypothalamus, whereas in ac cordance with the present study, the ME does not tend to reflect such changes [72. 73].…”

“…Hence, an indirect effect of GnRH neurones could be brought about by increased tone or synaptic input of an inhibitory peptide. In this regard, it is most relevant that intracerebroventricular administration of NPY inhibits LH secretion in OVX sheep [79] and NPY terminals con tact GnRH neurones in the POA in this species [80], and Obcr and Malven [55] reported increased NPY concen trations in the POA of ewes with reduced plasma LH caused by dietary restriction. The increased expression of NPY neurones [53] and the increased levels of NPY IR (present study) that are found in the hypothalamus of sheep on a restricted diet might be thought to be related to reduced levels of gonadotropin secretion.…”

“…In the ewe, NPY release as measured by push-pull perfu sion, was not changed at the level of the ME during peri ods of food restriction despite decreased GnRI I secretion [56. 70] and increased NPY in other hypothalamic re gions [55,72],…”

“…49] whereas central administration of NPY antiserum partially restores GH profiles in food-deprived rats [50]. At least some of the effects of NPY could be mediated through SRIH neu rones since there is an overlapping distribution of NPY and SRIH neurones in the ARC and intravenous GH administration activates c-Jos in these neurones in rats [51], Furthermore, in vitro studies in rats suggest that the reduction in GH secretion by NPY is mediated by a stim ulation of SRIH release [52], Although increased levels of NPY mRNA in the ARC [53], CSF [54] and other diencephalic regions [55] have been reported in nutritionally restricted sheep, the release of NPY within the ME was not changed [56], Hence, dif ferential regulation of peptidergic activity within discrete hypothalamic nuclei is evident but how this relates to gonadotropin secretion is not clear.…”

Feed Restriction in Prepubertal Lambs: Effect on Puberty Onset and on in vivo Release of Luteinizing-Hormone-Releasing Hormone, Neuropeptide Y and Beta-Endorphin from the Posterior-Lateral Median Eminence

“…7) of intact FR lambs. Increases in in vivo release of NPY after feed re striction have been reported from the paraventricular nu clei of intact lambs and adult ewes by this laboratory [28,29] and from the laterocerebrospinal fluid of FR adult ovariectomized sheep by another laboratory [48], How ever, since we and others [30,49] have recently reported an increase in tissue content of NPY in ME and all other hypothalamic structures, at this time the origin of the NPY increase in the cerebrospinal fluid is not clear.…”