Yoichi Kashio

Physiological Role of Somatostatin-Mediated Autofeedback Regulation for Growth Hormone: Importance of Growth Hormone in Triggering Somatostatin Release during a Trough Period of Pulsatile Growth Hormone Release in Conscious Male Rats

In mammals including human, it is generally accepted that growth hormone (GH) can regulate its own secretion through an autofeedback mechanism in which somatostatin (SRIF) may be involved. To explore a physiological role of SRIF-mediated GH autoregulation, the effect of exogenous human GH administration on plasma rat GH response to [D-Ala2, Nle27]-human GH-releasing hormone-(1-28)-agmatine (hGHRH-analog), which does not crossreact with anti-rat GH-releasing hormone gamma-globulin (GHRH-Ab), was examined in conscious male rats treated with GHRH-Ab in the absence and presence of anti-SRIF gamma-globulin (SRIF-Ab). Enhanced SRIF release during a trough period of natural pulsatile GH secretion, suggested by the blunted GH response to exogenous hGHRH-analog, no longer occurred when major GH secretory bursts were abolished by GHRH-Ab treatment. On the other hand, when hGH was administered in GHRH-Ab-treated rats so as to simulate the quantity and dynamic change of GH in hypophysial portal circulation in rats exhibiting pulsatile GH secretion, hGHRH-analog-induced GH rises were significantly suppressed during the period corresponding to a GH trough. This suppression was completely prevented by simultaneous treatment with SRIF-Ab. Furthermore, administration of bovine GH, but not ovine prolactin, resulted in significant suppression of hGHRH-analog-provoked GH rises. These findings suggest that enhanced SRIF release during a trough period of spontaneous GH secretory rhythm is induced by the preceding GH secretory burst, and also suggest a possible role for SRIF-mediated GH autoregulation in a physiological state.

Administration of antisera to vasoactive intestinal polypeptide and peptide histidine isoleucine attenuates ether-induced prolactin secretion in rats

The effect of immunoneutralization of endogenous vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI)-like peptides by administration of specific and potent antisera to the respective peptides on ether stress-induced prolactin (PRL) release was examined in male rats bearing an indwelling atrial catheter. Forty-five minutes after an injection of 1 ml of either normal rabbit serum (NRS), anti-VIP serum (AVS), anti-PHI serum (APS) or AVS plus APS, the rat was placed for 1 min in a beaker containing an ether-impregnated cotton ball. Ether exposure caused a prompt and significant increase in plasma PRL in all of the animal groups tested. Pretreatment with either antisera did not affect basal plasma PRL levels, whereas plasma PRL rises after ether exposure were significantly lower in rats pretreated with AVS, APS or AVS plus APS than those with NRS. These results suggest that hypothalamic VIP and PHI-like peptides may be involved, at least in part, in the mechanism by which ether stress stimulates PRL secretion in rats.

Calcitonin gene-related peptide-like immunoreactivity in the central nervous system and peripheral organs of rats

The concentrations of rat calcitonin gene-related peptide-like immunoreactivity (rCGRP-LI) in various organs of male rats as well as the molecular heterogeneity of rCGRP-LI in tissue extracts was examined using a specific radioimmunoassay (RIA) for rCGRP and gel-filtration chromatography. rCGRP-LI was high in extracts of the spinal cord (202 +/- 22.6 pg/mg wet wt. of tissue; mean +/- S.E.M.) and of the thyroid (229 +/- 62.3 pg/mg). rCGRP-LI was detectable in the brainstem, hypothalamus, stomach, duedenum, pancreas and kidney. The elution pattern of the extracts on a Sephadex G-50 column showed 3 peaks of rCGRP-LI irrespective of organs and tissues. The first peak corresponded to authentic rCGRP-(1-37). The second and third rCGRP-LI peaks probably consisted of C-terminal fragments of rCGRP, because they had a lower molecular weight than rCGRP-(1-37) and because our antiserum cross-reacts with a synthetic C-terminal fragment. The ratio of 3 rCGRP-LI molecules, however, differed between neural tissue extracts and others. The main component of rCGRP-LI in neural tissue was authentic rCGRP-(1-37), while the smaller fragments of rCGRP were chiefly contained in other tissues like the stomach, pancreas and thyroid. The relative ratio of rCGRP-LI molecules with different size in respective tissue extracts was not changed after leaving the dissected tissues for 2 h at room temperature. These findings indicate that rCGRP-LI is abundantly present in the thyroid as well as the spinal cord and it is detected in lower amounts in the alimentary tract and central nervous system. rCGRP-LI in the extracts consists of 3 different components, the proportions of which vary from one tissue to another, probably reflecting tissue-specific differences in the processing of CGRP.

Pituitary 1,25-dihydroxyvitamin D3 receptors in hyperthyroid- and hypothyroid-rats

The binding of 1 alpha,25-dihydroxy (26,27-methyl-[3H]) cholecalciferol ([3H]1,25-(OH)2D3) to its receptor in cytosol of the anterior pituitary cells was examined in hyperthyroid- and hypothyroid rats, as well as in normal rats. The binding capacity increased by 41% in L-Thyroxine-treated hyperthyroid rats and decreased by 49% in propylthiouracil-ingested hypothyroid rats as compared with normal control rats, whereas the affinity of the receptor for [3H]-1,25(OH)2D3 showed no difference among these 3 animal groups. These findings indicate that the number of 1,25(OH)2D3 receptors in the pituitary may be regulated by thyroid hormone, and further suggest that 1,25-(OH)2D3 may play some role in regulating functions of the anterior pituitary.