摘要:

In order to improve our understanding of the ligand specificity of somatostatin (SRIF) receptors in pituitary and brain, and to identify analogs that bind to one type exclusively, we compared several new SRIF analogs for competitive binding to pituitary and cerebral cortex membranes. Binding of [125I-Tyr11]SRIF to hypophysis and brain was of high affinity [KD = 0.76 nM (0.2–1.3) and 0.37 nM (0.1–0.8), mean (95% confidence limits)] and was characteristic of binding to one class of sites in both tissues. Competition by several SRIF analogs for such radioligand binding demonstrated that ligand specificity of adenohypophysial receptors was distinctly different from that of cerebral cortex. Two cyclic octapeptides D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 and D-Nal-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 bound to pituitary SRIF receptors with high affinity [Ki = 0.85 nM (0.5–1.2) and 0.35 nM (-0.3–0.9)] and were potent inhibitors of GH secretion from primary cultured pituitary cells [EC50 = 0.009 nM (0–0.02) and 0.017 nM (0.01–0.02), respectively]. However, these selective peptides did not compete (Ki ≧1 µM) for radioligand binding to brain. Amidation of the C-terminal end appeared to strikingly alter brain SRIF receptor recognition of the substituted ligand. Indeed, such amidation of the parent peptide, D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-OL (SMS 201–995) resulted in a reduced ability to displace labeled ligand from brain sites [Ki= 165.3 nM (47.6–282.9) to 842.2 nM (603.9–1,081)] but did not affect competition for pituitary receptors. Our results indicate that anterior pituitary SRIF receptors (SRIFa) have ligand specificities which are clearly different from those of their brain counterparts (SRIFa). Further, we have identified two potent SRIFa agonists which could be key ligands for studying interactions at the SRIFa receptor as well as being useful selecti

ISSN:0028-3835    

DOI:10.1159/000124788

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

We have longitudinally studied the effects of protein-deficient diet on serum growth hormone (GH) concentration in rhesus monkey. A biphasic basal GH response and a phenomenon of failure to suppress GH levels after glucose administration were observed in animals fed diet lacking proteins. GH levels remained consistently elevated in protein-deprived monkeys. Whether these elevations in GH will have any deleterious influence on the host remains to be seen.

ISSN:0028-3835    

DOI:10.1159/000124771

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

Hypothalamic α-melanocyte-stimulating hormone (α-MSH) was measured by radioimmunoassay in males after orchidectomy and after orchidectomy plus testosterone replacement, and in females after ovariectomy and after ovariectomy plus estradiol or progesterone, or estradiol and progesterone (EP) replacement. Gonadectomy inverted the diurnal rhythm of the α-MSH content observed in intact males in the medial basal hypothalamus (MBH) and preoptic hypothalamic area (POA), and produced a notable decrease of α-MSH total content in the three regions studied (MBH, POA and dorsolateral hypothalamus, DLH). The addition of testosterone restored the rhythm of the intact males and increased α-MSH content in MBH and POA. No diurnal variations in α-MSH content were observed in ovariectomized females. A circadian rhythm similar to that of proestrus was observed in MBH after estradiol or EP replacement, and in POA after the addition of any steroid. In DLH the injection of estradiol produced variations through the day, but they are somehow different from those described for proestrus. Treatment with progesterone significantly decreased α-MSH content in MBH and DLH, but not in POA. In this region an increase in α-MSH content was noticed after EP replacement. We conclude that gonadal steroids can alter the content of hypothalamic α-MSH and influence the diurnal variations of the peptide. This may be important in the modulation of several types of behavior or in the neuroendocrine control of gonado-tropin release in females, where α-MSH seems to modulate the release of luteinizing hormone and

ISSN:0028-3835    

DOI:10.1159/000124772

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

The effect of prolactin (PRL) on luteinizing hormone (LH) pulsation characteristics in intact and castrate male rabbits was investigated. Eight groups of animals were studied. Two groups of castrate and two groups of adult male rabbits served as controls to establish baseline pulsation characteristics. Preliminary studies showed that a sampling interval of 3–4 min was optimal. One group of castrate and one group of intact rabbits were sampled at this frequency for 60 min; two additional groups were sampled for 240 min. With these data determined, four groups were used in paired studies: two castrate and two intact groups received either a bolus injection intravenously of saline or PRL (20 µg), followed by a constant infusion of saline or PRL (50 µg/min) for 3.5 h. Blood was sampled every 3 min for the last 1.5 h of infusion. Serum LH was measured on each sample; rabbit PRL was measured on pooled samples. In selected samples bovine PRL was also measured. The LH pulsation characteristics of the 3 groups of castrate and intact controls (unper-fused and saline-perfused) were not statistically different and the data were pooled. The PRL-treated animals were compared to the controls. Castration increased LH mean concentration, pulse amplitude and duration. PRL infusion decreased mean LH concentration and pulse amplitude in both intact and castrate animals. Pulse duration was decreased significantly in castrate, but not in intact, animals by PRL infusion. We conclude that, in the adult male rabbit, PRL modulates LH pulsation. This action of PRL must occur either directly at the pituitary or more probably through an influence on gonadotropin-releasing hormone pulsation at the hypothala

ISSN:0028-3835    

DOI:10.1159/000124773

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

To investigate the existence of a dopaminergic preoptico-hypophyseal pathway in the goldfish, electrolytic lesions were placed in the rostral preoptic area and their effects on gonadotrophin levels and pituitary innervation examined. In a first experiment, the fish were sacrificed 2 days after surgery and the pituitary studied by electron microscopy. Numerous exocytosis profiles were observed in the gonadotrophs, confirming the large increase in serum gonadotrophin levels measured in the animals. In addition, type A and B degenerating fibers were detected in the neurohypophysis and the pars distalis, in particular at the level of the gonadotrophs. In the second experiment, the distribution of tyrosine hydroxylase-immunopositive fibers was studied in the pituitary of controls and lesioned animals. It was found that lesioning the anterior ventral preoptic region resulted in the disappearance of all positive fibers in the pars distalis, while those in the neurointermediate lobe appeared unaffected. The presence of a large group of catecholaminergic perikarya in the destroyed area was confirmed in control animals. These results and other data strongly support the existence of a dopaminergic preoptico-hypophyseal pathway, providing a morphological support for the inhibitory effect of dopamine on the release of anterior pituitary hormones in teleosts, in particular gonadotrophin.

ISSN:0028-3835    

DOI:10.1159/000124774

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

The arcuate nucleus-median eminence complex (AM) undergoes major structural and functional changes during normal puberty or if exposed to a pulse of estradiol in the prepuberal period. Those changes are expressed by increased synaptogenesis and by a drastic alteration in the feedback control of anterior pituitary gland hormone release. In this study we investigated the effects of estradiol benzoate (EB) on specific proteins in this hypothalamic area. Prepuberal, 25-day-old female rats were administered 10 µg of EB s.c. in oil or sesame oil vehicle. The animals were decapitated either 17 or 42 h after treatment. The brains were removed, blocked and serially sections at 300 µm using a Vibratome. The AM was dissected out and incubated for 6 h in a medium containing 35S-methionine and 35S-cysteine. Proteins from the AM were separated by two-dimensional gel electrophoresis, and the gels were exposed to X-ray film. The resulting autofluorographs were analyzed by scanning densitometry. The results show that the incorporation of labeled amino acids was increased in 10 proteins and decreased in 2 proteins in rats killed 17 h after EB. At 42 h after EB, 6 proteins showed an increased incorporation of amino acids and two proteins showed a decrease. Our results suggest that one or several of these proteins might be involved in the neuroendocrine and structural changes observed in the AM during pubert

ISSN:0028-3835    

DOI:10.1159/000124775

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

Anterior pituitary gland fragments were obtained from female Wistar-derived rats on dioestrus or pro-oestrus and perifused in Biogel columns in vitro. They were subjected at the beginning of each of 5 h of perifusion to a volley of 6 1-min pulses of luteinising hormone-releasing hormone (LHRH, 10 nM), given 4 min apart. Luteinising hormone (LH) was measured by radioimmunoassay in sequential 2-min fractions of the perifusate. Pituitary glands removed at 14.00 h on dioestrus showed a characteristic pattern of sensitisation followed by desensitisation to the repeated volleys of LHRH, whereas tissues removed at 10.00 or 14.00 h on pro-oestrus showed no evidence of desensitisation over the 5-hour period, the response to each LHRH volley being greater than the preceding one. Estradiol (E, 3–100 pg/ml) added to the medium from the start of perifusion had no significant effect on the pattern of response from tissues removed on pro-oestrus, but the highest concentration significantly enhanced the response of dioestrus pituitaries to all but the last of the LHRH volleys. Progesterone (P, 1–50 ng/ml) added to the medium produced a dose-related inhibition of the response of pro-oes-trous tissues to the LHRH volleys. Groups of animals were ovariectomised (OVX) on dioestrus and used for experiment the next morning. OVX at 10.00 h on dioestrus produced the pattern of response characteristic of dioestrus the next morning, but with much higher levels of LH release, which were unaltered by the addition of E to the medium. OVX at 17.00 h on dioestrus produced an entirely different pattern of response the next day, with high basal and moderate LHRH-induced LH release, and no evidence of changes in sensitivity of the tissue. In this case, E in vitro had a moderate enhancing effect. Various doses of E were injected subcutaneously immediately after OVX at 10.00 h on dioestrus; 1 µg/100 g body weight E had no effect on the subsequent pattern of response (sensitisation followed by desensitisation), but produced significantly greater LH release during the second, third and fourth volleys of LHRH; the pattern of LH release was also unaffected by P alone (2 mg per rat at 17.00 h after OVX), but the output throughout the perifusion was significantly reduced; 10 µg E completely changed the pattern, to one resembling that seen from tissues removed from intact pro-oestrus rats, but basal and LHRH-induced release were still markedly raised. 30 or 100 µg E reduced basal LH release to intact or sham-operated levels, but had no inhibitory effect on the high LHRH-induced release of LH. Both the pattern and magnitude of release were only restored to those exhibited by pituitaries from normal pro-oestrous animals when both 10 µg/100 g E and 2 mg P were given. In conclusion, these results suggest that this preparation is a suitable in vitro model for studying the mechanisms involved in the LH surge. Prolonged sensitisation to repeated LHRH stimulation is characteristic of pro-oestrous pituitaries, whereas dioestrus tissues show desensitisation. The pro-oestrous pattern could be restored in OVX animals by sufficient E replacement for 1 day, the addition of P replacement reducing the output of LH to

ISSN:0028-3835    

DOI:10.1159/000124776

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

Anterior pituitary gland fragments removed from Wistar-derived rats at 10.00 h on pro-oestrus were perifused with Krebs-bicarbonate medium in a column and exposed to hourly volleys of 6 1-min pulses of 10 nM luteinising hormone (LH)-releasing hormone (LHRH). LH release showed a characteristic pattern of prolonged (over 5 h) sensitisation to the releasing hormone, with the response to each volley becoming progressively greater. The addition of 2 mM difluoromethylornithine (DFMO; an inhibitor of ornithine decarboxylase) to the perifusion medium completely inhibited the response to all volleys of LHRH. This effect of DFMO was reversed by the concurrent inclusion of 2 mM putrescine in the medium. Putrescine alone had a small but non-significant enhancing effect on LHRH-induced release, and no significant effect on basal LH release in this system. In a second series of experiments, tissues were loaded with l-14C-ornithine and the radioactive carbon dioxide released into the medium during the perifusion monitored. Unstimulated pituitary tissues showed constant low levels of carbon dioxide release during 5 h of incubation, but those given hourly volleys of LHRH showed progressively increasing release of radioactivity, which was blocked by the addition of DFMO. No LHRH-stimulated increase in 14CO2 production from 1-14C-ornithine was seen from pituitary tissue removed at 10.00 h on dioestrus. Administration of DFMO (10–100 mg/rat) on the afternoon of pro-oestrus 4 h before the expected peak of the LH surge reduced the magnitude of the subsequent surge and the concentration of the hormone found in the anterior pituitary gland in a dose-related manner. In addition, the concentration of putrescine, but not of spermidine or spermine, was significantly reduced in treated animals (50 mg/rat) at the time of this attenuated surge. These results show that the prolonged sensitisation of pro-oestrous pituitary tissues in vitro to LHRHis correlated with increasing activity of ornithine decarboxylase, and that putrescine plays a permissive role in this sensitisation. This increase in ornithine decarboxylase activity appears to be necessary for the normal LH surg

ISSN:0028-3835    

DOI:10.1159/000124777

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

Activities of pineal N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase, involved in the biosynthesis of melatonin from serotonin, were assessed over 24 h in the pineal organ of pikes (Esox lucius, L.; teleosts) entrained to natural (winter) environmental conditions. Only NAT activity exhibited daily changes, rising at the onset of darkness and resuming low values shortly before the end of the scotophase. The rhythm was damped under constant darkness, lower and higher values being shifted towards intermediate ones. NAT activity was lowered under constant light; however, a significant increase was seen at the end of the subjective night, suggesting the existence of a low-amplitude rhythm. Illumination of the pikes at the middle of the scotophase induced inactivation of roughly half of the maximal NAT activity, possibly indicating the existence of one photolabile and one photostable enzymatic component. Under natural conditions, radioassayable melatonin of the pike pineal organ displayed daily variations which paralleled those of NAT activity. Melatonin production thus appears to reflect the daily changes of NAT, synchronized to the light/dark cycle.

ISSN:0028-3835    

DOI:10.1159/000124778

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

Progestin receptors have been detected in the brain and pituitary of gonadectomized hamsters using the synthetic ligand (3H)R5020. The number of receptors found in males and females could be dramatically increased by priming the animals with estradiol benzoate 48 h before the binding was measured. Total progestin-binding activity in the cortex, hypothalamus-preoptic area and pituitary of both sexes was the same when high doses of estrogen (30 µg per animal) were used for induction, but the inducibility of the male receptors was found to decline with time after gonadectomy. These findings are discussed in relation to the effects of progesterone on aggressive and sexual behaviors in gonadectomized hamsters

ISSN:0028-3835    

DOI:10.1159/000124779

出版商:S. Karger AG    

年代:1987

数据来源: Karger