Effects of estrogen on growth hormone pulsatility in peripheral blood and neuropeptide profiles in the cerebrospinal fluid of goats.

We previously reported that growth hormone (GH) pulses were negatively associated with neuropeptide Y (NPY) profiles in cerebrospinal fluid (CSF) of the third ventricle of Shiba goats. In addition, while most GH pulses were coincident with GH-releasing hormone (GHRH) pulses, there was no correlation between GH and somatostatin (SRIF) levels. The present study was performed to elucidate the relationship between GH pulses and these neuropeptide levels in CSF when estradiol (1.0 mg/head) was subcutaneously administered to ovariectomized goats. CSF and plasma samples were collected every 15 min for 18 h (from 6 h before to 12 h after injection). GH levels in peripheral blood and GHRH, SRIF and NPY levels in CSF were measured by radioimmunoassay. Pulse/trough characteristics and correlations were assessed by the ULTRA algorithm and cross-correlation analysis. Before estradiol was injected, significant coincidence was found between GHRH pulses and GH pulses, and negative coincidence was found between NPY troughs and GH pulses. Six to 12 h after estradiol injection, the amplitude and area under the curve (AUC) of the GH pulses were markedly increased. The duration and AUC of the GHRH pulses in the CSF were also increased, and stronger synchrony of GHRH with GH was observed. In contrast, the baseline of NPY was significantly decreased, and the negative correlation between the GH pulses and NPY troughs disappeared. The parameters of SRIF troughs were not clearly changed. These observations suggest that estrogen enhances the pattern of secretion of GH in the goat via enhancement of GHRH pulses and decrease of NPY levels.

Negative correlation between neuropeptide Y profile in the cerebrospinal fluid and growth hormone pulses in the peripheral circulation in goats.

BACKGROUND/AIMS: Growth hormone (GH) is secreted in pulsatile fashion, but the involvement of neuropeptides in the generation of GH pulses is not fully understood. The present study was conducted to elucidate the relationship between GH pulses and neuropeptide levels in the cerebrospinal fluid (CSF) of the third ventricle in ovariectomized goats. METHODS: CSF and plasma samples were collected every 15 min. Levels of plasma GH and profiles of GH-releasing hormone (GHRH), somatostatin (SRIH) and neuropeptide Y (NPY) in the CSF were measured by radioimmunoassay. Pulse/trough characteristics and correlations were assessed by the ULTRA algorithm, cross-correlation analysis and approximate entropy test. RESULTS: The periodicity of GH pulses was 2.20 h. Although most GH pulses were associated with GHRH peaks, there was no correlation between GH and GHRH or GH and SRIH. NPY levels in the CSF fluctuated episodically at 2.03-hour intervals. GH pulse peaks occurred 0-30 min after NPY troughs, and there was a significant negative cross-correlation and negative synchronicity between GH and NPY profiles. In addition, intracerobroventricular infusion of NPY suppressed GH secretagogue (KP102)-induced GH release. CONCLUSION: The periodic decrease in NPY may be involved in the generation of GH pulsatility in goats.

Modulation of growth hormone pulsatility by sex steroids in female goats.

GH is secreted in a pulsatile manner, the pattern of which plays an important role in the regulation of growth and metabolism. Sex steroids are also known to participate in metabolic regulation. The present study was undertaken to elucidate the relationship between changes in GH pulsatility and metabolic transition during the estrous cycle in goats. From ovariectomized (OVX) and intact females in the early luteal, late luteal, and follicular phases, blood samples were taken every 15 min for 24 h, and plasma GH was measured by RIA. In the early luteal phase, GH was secreted in a distinct pulsatile manner, the pattern of which was similar to that in OVX goats, whereas the GH pulse frequency, amplitude, and area under the curve (AUC) were decreased in the late luteal phase. In the follicular phase, the GH pulse frequency, amplitude, and AUC were significantly larger than those in the late luteal phase. The regularity of GH pulsatility was highest and lowest in the early and late luteal phases, respectively. Both IGF-I and free fatty acid levels in the plasma were higher in the follicular than the luteal phase. Subcutaneous injection of estradiol to OVX goats increased the GH pulse amplitude and AUC, whereas the implantation of progesterone for 5 d decreased those parameters. These results suggest that the pulsatile pattern of GH secretion in goats varies with sex steroid levels and thereby affects IGF-I secretion and lipolysis during the estrous cycle.