Islet release of ACTH-like peptides and their modulatory effect on insulin secretion.
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Biomedical subjects
Publications and source records attributed to F Estivariz.
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The stimulatory effect of prolactin on sexual accessory glands is well established, though the mechanism of trophic action remains poorly understood. We have therefore assessed the effect of high levels of prolactin on ornithine decarboxylase activity and polyamine content in seminal vesicles (SV) of adult rats. Hyperprolactinaemia was induced by implantation of tissue fragments of a prolactin-secreting tumour 7315a, and the rats killed at 35 days post-inoculation. Serum levels of prolactin were increased significantly (p < 0.001) in tumour-bearing rats. Levels of testosterone in serum were reduced markedly, whereas LH levels remained unchanged. SV weight in the experimental group was not significantly different from that in the corresponding control group. A clear increase in ornithine decarboxylase activity of SV was observed (p < 0.001) in the hyperprolactinaemic rats. However, there was no change in the polyamine content of SV in tumour-bearing rats, compared to the control group. These results indicate that ornithine decarboxylase activity in SV of adult rats is regulated mainly by prolactin. This experimental model may be useful for identification of some of the events involved in the trophic action of prolactin.
After bilateral superior cervical ganglionectomy (SCGx) in adult male rats, norepinephrine content of the pituitary neurointermediate lobe (NIL) decreased at 12-24 h after surgery to attain concentrations 40-60% of controls between 24 and 60 h after surgery. To assess arginine vasopressin (AVP) secretion during this time, plasma and NIL-AVP levels were measured by radioimmunoassay. In sham SCGx controls, plasma AVP increased about 2-fold within 6 h after surgery and decreased thereafter, to attain presurgical values by 60 h after surgery. In SCGx rats, a significant increase in plasma AVP concentration was observed at the 6th h after surgery, as compared to presurgical concentrations, with a decrease to values significantly lower than those of presurgical controls at 16-18 h after SCGx. As compared to sham-operated rats, significantly higher plasma AVP levels 6 h after surgery and significantly lower plasma AVP levels 16-24 h after surgery were found. NIL-AVP concentration in SCGx and sham-operated ras were significantly lower than presurgical levels at 6 h after surgery. SCGx rats had significantly higher amounts of AVP in NIL at 16-24 h after surgery. The changes in plasma and NIL-AVP levels found 6 or 16 h after SCGx or sham SCGx were unaffected by a prior pinealectomy. Two injections of the alpha 1-adrenoceptor blocker prazosin 45 and 90 min before sacrifice, alone or together with the beta-blocker propranolol, prevented the increase in plasma AVP found in SCGx rats 6 h after surgery, and the decrease in plasma AVP and the increase of NIL-AVP found 16 h after SCGx.(ABSTRACT TRUNCATED AT 250 WORDS)
The changes in adrenocorticotropin (ACTH) release before, during and after sympathetic nerve degeneration following superior cervical ganglionectomy (SCGx) were examined in male rats. A 12-fold increase of circulating ACTH was found in both SCGx and sham-operated rats 6 h after surgery. In sham-operated rats, plasma ACTH decreased by about half 16-22 h after surgery, whereas in SCGx rats it remained at a high concentration from 16 to 54 h after surgery, attaining basal values by 120 h post-SCGx. In SCGx rats, MBH corticotropin-releasing hormone (CRH) content decreased significantly from 16 to 54 h after surgery, while in controls it remained unmodified. Significantly smaller arginine vasopressin (AVP) contents were found in MBH of SCGx rats as compared to sham-operated controls, 16-54 h after surgery. In rats exposed to ether or immobilization stress 22 h after SCGx, plasma ACTH levels were significantly higher than in controls; however, since unstressed ACTH levels were about twice as high in SCGx rats, the percent increase of ACTH was smaller in the SCGx group. A decreased response of plasma ACTH to ether or immobilization stress was found in rats 7 days after SCGx. In rats subjected to a simultaneous adrenalectomy (Adx) and SCGx or sham-SCGx, plasma ACTH levels increased to a similar extent in both groups. ACTH increase after Adx was accompanied by decreases in MBH CRH, and absence of significant changes in MBH AVP contents. Rats subjected to pinealectomy (Px) or sham-Px 1 week earlier and killed 22 h earlier exhibited similar responses in plasma ACTH and MBH CRH to SCGx regardless of pineal intactness.(ABSTRACT TRUNCATED AT 250 WORDS)
We have studied the regulation of adrenal function in male rats treated neonatally with monosodium glutamate (MSG) and in littermate controls. When 6-7 months old, MSG-treated rats presented reduced body, adrenal and pituitary weight, obesity, atrophy of the optic nerve and damage of the arcuate nuclei (ARN) of the hypothalamus. MSG-treated rats showed increased serum corticosterone (CORT) levels under resting conditions; after ether stress the increase in serum CORT was greater in MSG animals when compared to littermate controls. Plasma ACTH followed the same trend although it reached significance after ether stress only. Both circulating CORT and ACTH were normally suppressed by dexamethasone (DEX) administration. Levels of corticosteroid binding globulin were also increased, whereas daily circadian rhythm of serum CORT was blunted. We also determined cytosolic receptors in areas suggested to participate in the negative feedback of glucocorticoids at the central level. Binding of (3H)-DEX in MSG rats was similar to controls in hippocampus, whole hypothalamus and anterior pituitary, but a significant reduction (approximately equal to 50%) was obtained after microdissection in the area normally occupied by the ARN, without changes in the ventromedial nuclei of the hypothalamus. These results suggest that the ARN may be involved in the regulation of the pituitary-adrenal axis, although the abnormalities observed in the MSG syndrome partially differ from those in rats with hippocampal damage, previously studied in our laboratory.
Pro-opiocortin, the precursor of ACTH, LPH and gamma-MSH, is biosynthesized in both the cells of the pars intermedia and the corticotrophs of the pars distalis. In the pars distalis its processing does not vary significantly from species to species whereas in the pars intermedia large differences occur. The release of ACTH, beta-LPH and pro-gamma-MSH from the corticotrophs is under common positive control by hypothalamic corticotropin-releasing factor (CRF) and the nature of the peptides remains unchanged when they are secreted. The release of all five pars intermedia peptides that we have measured in vitro appears to be under tonic dopaminergic inhibition. The secreted peptides have also been identified chromatographically. The lack of unequivocal physiological function in the periphery, the diversity of the pars intermedia peptides and this common control mechanism tend to preclude a simple endocrine role for the pars intermedia. The neural effects of MSH and endorphin are well documented and specific neuronal uptake therefore cannot by dismissed. The absence of pars intermedia in the adult human pituitary suggests that such a site of synthesis of these peptides plays a minor role in learning and behaviour in a species (such as Homo sapiens) that has a highly evolved intelligence and may, instead, need to synthesize the peptides only in the brain.
Two cystine-containing peptides isolated from human pituitaries were partially sequenced. The peptides are fragments derived from the amino-terminal of pro-opiocortin (NPOC) and have been chemically characterized as NPOC 1-28 (which lacks gamma-MSH) and NPOC 2-59. Their availability enables us to investigate new putative biological roles for the amino-terminal conserved sequence of pro-opiocortin.
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