38 research outputs found
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On the Half Life of Thyrotropin-Releasing Hormone in Rats
After the injection of 14C-labeled TRH into normal male rats, radioactivity disappeared rapidly from the circulation. The half life of 14C-TRH was found to be 4.16 min; however, the true half life of TRH may be masked, since TRH is rapidly inactivated in the blood to compounds having similar chemical structures and probably similar half lives. Chromatography of methanol extracts of plasma samples taken at 1, 2, and 6 min revealed that some of the radioactivity had the same Rf value as that of TRH, while other areas corresponded to the free acid of TRH (pyro-glu-his-pro-OH), glu-his-pro, and his-pro-NH2. The mean volume of distribution of TRH in our studies was 18.5% of the body weight. Approximately 25% of the radioactivity was excreted into the urine within 60 min after the intravenous injection of 1 µCi of 14C-TRH. Urinary radioactive metabolites appeared to have the same electrophoretic mobilities as TRH and the free acid of TRH
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Lipid mobilizing factor from the hypothalamus
Mouse epididymal fat pads were incubated for 2 hours in 3 per cent albumin Krebs-Ringer phosphate buffer (KRP), free of calcium and glucose, or in Krebs-Ringer bicarbonate (KRB) containing calcium. Addition of defatted acetic acid extracts of pituitary stalk and median eminence (SME) of ovine, porcine, bovine and human orgin significantly increased lipolysis as measured by release of glycerol into the KRP incubation medium and inhibited 1-
14C acetate incorporation into lipids. Extracts of porcine SME were the most potent in enhancing glycerol release and showed a log-dose response relationship between 0.1 mg. to 1.0 mg. extract/ml. of medium. Extracts of cerebral cortex from all the species tested were without effect on lipolysis at these dose levels. After gel filtration of porcine SME extracts on Sephadex G-25, lipolytic activity emerged in an area occupied by peptides with molecular weight of 3000 to 5000. The same area contained ACTH-like activity (200 mU./mg.). A comparison of the in vitro lipolytic activity of this hypothalamic fraction indicated that it was active in doses as small as 20 μg./ml. when incubated in KRP with mouse, rat, and hamster fat pads. Higher doses (40 μg./ml.) were required to elicit a lipolytic response from rabbit and guinea pig tissue. Incubation of the hypothalamic fraction with trypsin and chymotrypsin abolished the lipolytic response while pepsin had no effect. Chemical analyses of this hypothalamic fraction showed it to be free of calcium and norepinephrine and its lipolytic activity could not be accounted for by contamination with TSH, oxytocin, vasopressin, α and β-MSH or hypothalamic releasing factors. Most, but not all, of the lipid mobilizing activity of the porcine fraction may be accounted for by ACTH and/or its analogues with adrenocorticotropic activity
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Effect of thyrotropin (TSH)-releasing factor (TRF) on plasma TSH levels in nutria ( Myocastor coypus)
Intrapituitary or intracarotid infusion of porcine thyrotropin-releasing factor (TRF) into coypu (nutria) failed to increase plasma thyrotropin (TSH) levels. Intravenous administration of TRF into thyroidectomized nutria resulted in an increase in plasma TSH, but the responses were inconsistent. The increase in plasma TSH after TRF was readily demonstrable when thyroidectomized nutria were pretreated with small doses of triiodothyronine. Low sensitivity of the nutria to exogenous TRF may be ascribed, in part, to the relatively low TSH levels in the anterior pituitary gland. These studies nevertheless indicate that TRF can increase plasma TSH levels in the nutria and extend to one more species the evidence of responsiveness to TRF
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Distribution, Half-Life, and Excretion of 14C- and 3H-Labeled L-Prolyl-L-Leucyl-GIycinamide in the Rat
H-Pro-Leu-Gly-NH2, a potentinhibitor of melanocyte stimulating hormone (MSH) release [MSH-release inhibiting factor (MIF)], was labeled with 14C-leucine or 3H-proline and injected i.v. into rats. H-Pro-14C-Leu-Gly-NH2 was found to have a half-life of approximately 9 min and to be distributed in a space greater than that of the plasma volume. Relatively little radioactivity and no intact H-Pro-Leu-Gly-NH2 could be found in the urine 1 h after administration. 3H- and 14C-labeled-H-Pro-Leu-Gly-NH2 accumulated in the pineal, pituitary, kidney, liver, and adrenals; the elevated tissue to plasma ratio in the pineal, along with the identification of unchanged H-Pro-Leu-Gly-NH2 there, suggests the possibility of a direct influence of the hypothalamus upon the pineal gland
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Studies on Retarded Growth of Rats with Hereditary Hypothalamic Diabetes Insipidus
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Effect of Monosodium Glutamate on Some Endocrine Functions
Neonatal female and male rats of the Sprague-Dawley strain were injected subcutaneously with a daily dose of MSG (2.2–4.2 mg/g body wt.) beginning on the 2nd day of life. The rats were autopsied at 40 and 110 days of age. At 40 days of age, the body weight and nasoanal lengths were significantly reduced in the MSG-treated rats. At 110 days, the body lengths of MSG-treated rats were approximately 10–12% shorter than those of control rats, and calculation of the ‘Lee’ index indicated a significant increase in carcass fat. Food consumption studies, carried out at 75 days of age, showed a significant hypophagia in some MSG-treated rats. Upon autopsy at 40 days of age, the absolute weights of the thyroid and adrenal glands of both sexes were significantly decreased from those of control rats; but when corrected for body weight, these differences were marginal. At 110 days, the absolute weights of the adrenal and thyroid glands of both sexes were significantly reduced from their respective control levels. Gonadal weights of MSG-treated rats were significantly reduced at 40 and 110 days of age. Size and weight of the anterior pituitary glands of both male and female MSG-treated rats were significantly reduced from control values. There was a marked decrease in growth hormone and luteinizing hormone content in the anterior pituitaries of male and female MSG-treated rats at 40 days. However, thyrotropin content of the anterior pituitary of MSG-treated male rats did not show any significant change from control levels at 40 days of age
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Treatment of experimental ovarian carcinoma with monthly injection of the agonist D-Trp-6-LH-RH: A preliminary report
Hormones, particularly gonadotropins, have been implicated in the development of ovarian cancer. Chronic administration of agonistic analogs of luteinizing-hormone releasing-hormone (LH-RH) induces an inhibition of the pituitary-gonadal axis. The blockade of the release of luteinizing-hormone and follicle-stimulating hormone (FSH) may exert a possible therapeutic effect on ovarian cancer. We examined the results of prolonged administration of D-Trp-6-LH-RH, an agonistic analog of LH-RH in experimental ovarian cancer. We used the recently developed ovarian cancer model in rats, which is produced by treatment of pregnant rats with
N-nitrosobis(2-oxopropyl)amine (BOP), following which a high incidence of ovarian tumors are induced in the offspring. In morphologic aspects the induced tumor resembles human ovarian neoplasms. Once a month administration of a delayed release preparation of microcapsules of D-Trp-6-LH-RH prolonged the survival and decreased tumor growth and the incidence of metastases. Additional experimental and clinical studies are needed to determine the efficacy of the treatment with LH-RH analogs in ovarian cancer