摘要:

In order to better understand the mechanisms underlying the reduction in growth hormone (GH) secretion in diabetic rats, we studied hypothalamic somatostatin secretion both in vivo (into hypophysial portal blood) and in vitro (from hypothalamic fragments) 5,9 and 30 days after induction of diabetes. Experimental diabetes was induced by an intraperitoneal injection of streptozotocin (STZ) at a dose of 65 mg/kg. Basal plasma GH was significantly reduced in diabetic rats at all stages. Somatostatin levels in hypophysial portal blood was unaffected in 5-day STZ-diabetic rats and significantly increased 9 days after STZ administration. Chronic insulin replacement therapy in diabetic animals partly normalized somatostatin levels as well as plasma GH and glucose levels. A good correlation was observed between in vivo and in vitro experiments. Indeed, somatostatin release from hypothalamic fragments did not change 5 days after STZ-induced diabetes and significantly increased 9 and 30 days after STZ administration. The in vitro increase in hypothalamic somatostatin secretion was observed in 10 as well as in 33 mM glucose concentration in the incubation medium. In the same experiment, the in vitro hypothalamic corticotropin-releasing factor secretion was lowered 5 and 9 days after diabetes induction. We conclude that hypothalamic somatostatin release increases in diabetic rats. These changes may contribute to the reduction in GH secretion in these animals. However, since these changes occur after the onset of plasma GH decrease, a factor(s) other(s) than somatostatin may play a causal role in the reduction in GH secretion.

ISSN:0028-3835    

DOI:10.1159/000126161

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Regulation of phosphoinositide (PI) signaling through the muscarinic cholinergic receptors (mAChRs) and their possible role were explored in the rat pineal gland. A sensitization of the PI signaling pathway was seen with advancing age. Binding of the mAChR ligand [N-methyl-3H]scopolamine to pineal sections, as detected by autoradiography, significantly decreased with advancing age and thus negatively correlated with the gland’s ability to respond to cholinergic stimulus. The cholinergic agonist carbachol induced a time-dependent desensitization of the muscarinic PI signaling after 2 h of pretreatment in vitro (43 and 61 % dampening of the PI response after 2 and 11 h pretreatment, respectively). This homologous desensitization was not mimicked by forskolin or phorbol esters, suggesting that proteins kinases A and C were not involved. Carbachol stimulation of the pineal glands in vitro increased melatonin release 2-fold, an effect quantitatively similar to that seen after adenylyl cyclase activation. Carbachol failed, however, to affect pineal cAMP levels. These results suggest that the PI signaling through pineal mAChRs is desensitized in young rats, possibly due to higher exposure to endogenous acetylcholine. Thus acetylcholine might play a prominent role in the developing gland. Moreover, acetylcholine could modulate melatonin release from the adult pineal gland in viv

ISSN:0028-3835    

DOI:10.1159/000126162

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Growth hormone (GH) secretion is blunted in diabetic rats. In the present experiment we observed that pituitary GH concentrations and the plasma GH response to an exogenous dose of growth hormone-releasing hormone (GHRH) is decreased in streptozotocin-induced diabetic rats (p < 0.02) with respect to normal rats. In an attempt to determine if increased somatostatin (SRIF) secretion is responsible for the decreased GH secretion, we studied the effect of modulating SRIF tone on the GH response to GHRH in normal and streptozotocin-induced diabetic rats. Rats were pretreated with either normal sheep serum and saline (NSS + SAL), somatostatin antibodies (SRIF-Ab), or pyridostigmine (PD), an acetylcholinesterase inhibitor hypothesized to reduce hypothalamic SRIF secretion. Pretreatment of normal rats with SRIF-Ab or PD resulted in an increased GH response to exogenous GHRH in comparison to NSS + SAL-pretreated normal rats at 5 min postinjection. In contrast, pretreatment of diabetic rats with SRIF-Ab or PD did not alter the GH response to exogenous GHRH when compared to NSS + SAL-pretreated diabetic animals. These results suggest that the blunted GH response to exogenous GHRH observed in streptozotocin-induced diabetic rats may not be due to an increase of endogenous SRIF tone.

ISSN:0028-3835    

DOI:10.1159/000126163

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

In the present study we investigated the effects of modulating endogenous somatostatin (SRIF) on the GH response to growth hormone-releasing hormone (GHRH) in spontaneously diabetic BB/Wor rats and nondiabetic littermates. Plasma growth hormone (GH) concentrations following injection of GHRH (500 ng/kg, i.v.) were measured in the rats after pretreatment with either normal sheep serum + saline (NSS + SAL), somatostatin antibody (SRIF-Ab), or pyridostigmine bromide (PD), an acetylcholine esterase inhibitor hypothesized to decrease hypothalamic SRIF tone. The GH response to GHRH in spontaneous diabetic rats pretreated with NSS + SAL was significantly lower (p < 0.05) than the response observed in the nondiabetic group. SRIF-Ab pretreatment reversed the blunted GH response observed in the diabetic rats. However, PD pretreatment was not effective. These results indicate that the blunted GH response observed in BB/Wor diabetic rats is reversed by neutralization of endogenous SRIF with SRIF-Ab and leads to the conclusion that SRIF plays an active role in modulating GH secretion in spontaneously diabetic rats. The failure of PD to modulate the GH response suggests this acetylcholine agonist is ineffective in this animal paradigm.

ISSN:0028-3835    

DOI:10.1159/000126164

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Developmental patterns of aromatase activity (AA) were characterized in individual forebrain regions of the rat at gestational day (GD) 22 and postnatal days (PN) 6 and 15. Aromatase activity was measured separately in homogenates of left and right preoptic area, anterior amygdaloid area, medial amygdaloid nucleus, anterior hypothalamic area and posterior hypothalamic area, by the tritiated water method with [1β-3H]-androstenedione as a substrate. Region- and sex-dependent asymmetries of AA with either left-to-right or right-to-left gradients were found. They change between GD22 and PN6 and PN15 according to region-specific patterns. Thus, AA of the male medial amygdaloid nucleus of the left side is higher at GD22, lower at PN6 and equal to the right side at PN15; in females, AA of the left side is lower than AA of the right side at GD22 and higher at PN6 and PN15. In preoptic area, a side difference (left side higher) was only detected in males. Asymmetries may result from differences in the expression of the enzyme by individual cell groups, or from differences in the number of cells per area expressing the enzyme. In either case, the stage-dependent patterns of asymmetry in AA would be expected to influence sex steroid-dependent differentiation processes in individual forebrain areas

ISSN:0028-3835    

DOI:10.1159/000126165

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Nicotinic cholinergic, opiate and serotonergic agonists as well as dopaminer-gic antagonists induce the release of pituitary prolactin. The purposes of the present studies were to determine if nicotine, morphine and the serotonin 1A (5-HT1A) agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) utilize a common synaptic pathway to release prolactin and, if so, to establish the serial order of the receptors involved. We also sought to determine whether the pathway under investigation leads to the secretion of prolactin via a mechanism involving dopamine, the prolactin inhibitory factor. Male rats with indwelling jugular catheters were pretreated with saline, mecamylamine, naltrexone, methysergide or bromocriptine. In the saline-treated animals, administration of nicotine, morphine, 8-OH-DPATand haloperidol resulted in significant increases in plasma prolactin levels. Mecamylamine pretreatment prevented the prolactin response to nicotine only. N-altrexone blocked the stimulation of prolactin release by morphine and by nicotine. Methysergide inhibited the effects of 8-OH-DPAT, morphine and nicotine but not haloperidol. Bromocriptine blocked the prolactin secretion induced by haloperidol as well as by each of the above agonists. Also, in dual-immunocytochemically stained sections, tyrosine hydroxylase-immunoreactive cells and serotonin-immunoreactive processes were detected in close anatomical proximity in the dorsomedial arcuate nucleus. These data indicate that nicotine, morphine and 8-OH-DPAT act to release prolactin via a common synaptic pathway expressing nicotinic cholinergic, opiate, and 5-HT1A receptors at synapses arranged serially in that functional order. Furthermore, the data indicate that the in vivo secretion of prolactin via this pathway may ultimately occur through the inhibition of dopamine release.

ISSN:0028-3835    

DOI:10.1159/000126176

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The photosensory pineal organ of teleost fish shows a circadian rhythm in melatonin synthesis, and melatonin is known to influence a number of physiological functions. However, the target sites for melatonin are not known. We have investigated the distribution of melatonin binding sites in the brain of the salmon, Salmo salar. Brains were collected for receptor binding assay and autoradiography at each of three time points: just after lights on, just before lights off, and in the dark at midnight (photoperiod light-dark 12:12, lights on at 08.00 h, lights off at 20.00 h). Specific binding of 2-[125I]iodomelatonin was observed in several brain areas. High densities were associated with (1) the optic tectum, (2) the preoptic area, (3) an area encompassing the magnocellular superficial pretectal nucleus (‘nucleus rotundus’) and the glomerular complex, (4) the inferior lobes of the hypothalamus, (5) the lateral mesencephalic tegmentum including the torus semicircularis, and (6) the molecular layer of the cerebellum. No binding was observed in the pineal organ or in the pituitary. We observed no differences in labeling between brains collected at different time points, except in the preoptic area where binding was high at 20.00 and 24.00 h, but low at 08.00 h, and in the corpus cerebelli, where labeling in the molecular laver was higher at 24.00 and 08.00 h than at 20.00 h. Saturation experiments with crude brain membranes indicated the presence of a single binding site with no significant differences related to the time of day, with Kd values ranging from 30 to 54 pM, and Bmax values from 7.0 to 10.8 fmol/mg protein. Nonspecific binding, determined with 0.1 µM melatonin, was <20%. The Kd and Bmax values are in the same range as those reported for the so-called high-affinity binding site in mammalian neural ti

ISSN:0028-3835    

DOI:10.1159/000126166

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Oxytocin-induced LH release from dispersed rat anterior pituitary cells in vitro was shown to be dependent on the steroidal environment. Preincubation of anterior pituitary cells with estradiol for 48 h enhanced the subsequent LH response to oxytocin (p < 0.001). Maximal sensitization was observed with estradiol at 1 nM. Release of LH induced by oxytocin was inhibited in the presence of progesterone or to a greater extent in the presence of equimolar testosterone. Complete suppression of oxytocin-induced LH secretion occurred with 1 nM progesterone. Incubation of hemipituitaries with oxytocin revealed that the pituitary was sensitive in vitro to oxytocin at proestrus (p < 0.05) but not at other stages of the cycle. The results indicate that there is altered sensitivity to oxytocin of the pituitary at different stages of the estrous cycle. Therefore activity of the neuropeptide in vivo might be modulated by steroids.

ISSN:0028-3835    

DOI:10.1159/000126167

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

In situ hybridisation histochemistry and immunohistochemistry was used to study the response of the noradrenergic A6 and A2 cell groups in the rat following oral administration of 2% saline for 12 days. Messenger ribonucleic acid (mRNA) encoding tyrosine hydroxylase and neuropeptide Y increased by 85 and 65%, respectively (p < 0.05) in A6, while levels in A2 were unaltered after saline ingestion. The observed changes in mRNA were accompanied by increased expression of neuropeptide Y and tyrosine hydroxylase immunoreactivities in A6 neurons, whereas A2 neurons were unaffected. In contrast, mRNA encoding galanin, which is also colocalised with noradrenaline in A6 cells, was unaltered by osmotic stimulation. Our results suggest that noradrenaline and neuropeptide Y transmitter systems in the A6 group are activated whereas the galanin transmitter system remains unaffected during saline ingestion.

ISSN:0028-3835    

DOI:10.1159/000126168

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The effects of lesions (x) of the suprachiasmatic nucleus (SCN) or paraventricular nucleus (PVN), or pinealectomy (PINX) on gonadal recrudescence, body and fat pad weights, and food intake were examined in photoregressed male Siberian hamsters (Phodopus sungorus sungorus). Blood was sampled weekly for serum follicle-stimulating hormone (FSH) and prolactin (PRL) measurement. Lesions were classified as complete if greater than 80% of the nuclei were destroyed and designated as ‘hits’, whereas incomplete lesions were designated as ‘misses’. Five weeks postlesion, hamsters with PVNx or SCNx hits and SCNx misses (lesions generally located caudal and dorsal to the SCN) had increased testes, epididymal white adipose tissue and body weights, increased food intake, and progressively increasing serum PRL, but not FSH concentrations compared with PINX, PVNx misses and intact short day controls. SCNx hamsters with complete lesions had sparse or arrhythmic locomotor activity patterns in subsequent tests under constant conditions. Although no single area was identified histologically as the locus for this effect, the hyperprolactinemia and rapid gonadal recrudescence was consistent with varied degrees of damage to the periventricular area. These results suggest a novel central control of PRL secretion by an area caudal and dorsal to the SCN, and extending to and including the PVN. This area may be involved with maintaining short day re

ISSN:0028-3835    

DOI:10.1159/000126169

出版商:S. Karger AG    

年代:1992

数据来源: Karger