摘要:

We studied the effects of the histamine H1 receptor antagonists diphenhydramine and pyrilamine, the H2 receptor antagonist ranitidine and the muscarinic receptor antagonist atropine injected into the third cerebral ventricle on prostaglandin F2α (PGF2α)-induced hyperglycemia in anesthetized fed rats. The concomitant injection of diphenhydramine (1 × 10–8, 5 × 10–8 mol) with 50 µg PGF2α significantly suppressed the increase in hepatic plasma glucose concentrations induced by PGF2α The concomitant injection of 1 × 10–8 mol pyrilamine with 50 µg PGF2α did not suppress the above-mentioned parameter, while 5 × 10-8 mol pyrilamine significantly suppressed it. Diphenhydramine suppressed the PGF2α-induced hyperglycemia to a greater extent than did pyrilamine. In contrast, concomitant injection of the H1 receptor antagonist ranitidine (1 × 10–8, 5 × 10–8 mol) did not suppress the hyperglycemia induced by PGF2α. The concomitant injection of 5 × 10–8 mol diphenhydramine or pyrilamine with 50 µg PGF2α significantly suppressed the increase in plasma epinephrine induced by PGF2α, but the same dose of ranitidine had no effect. The concomitant injection of atropine (5 × 10–8, 5 × 10–7 mol) with 50 µg PGF2α significantly suppressed the increase in hepatic plasma glucose and epinephrine induced by PGF2α. These findings demonstrate that PGF2α-induced hyperglycemia is mediated by the muscarinic receptors of cholinoceptive neurons and in part by H1

ISSN:0028-3835    

DOI:10.1159/000126354

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Chronic hyperprolactinemia in the rat is associated with suppression of plasma gonadotropin concentrations. The reduction of gonadotropins is considered to be due to either an inhibitory effect of prolactin (PRL) on pituitary gonadotropin secretion and/or suppression of hypothalamic gonadotropin-releasing hormone (GnRH) release. In contrast to the in vivo effects of PRL on hypothalamic GnRH release, it has recently been reported that endogenous hypothalamic PRL exerts a tonic stimulatory effect on GnRH release in vitro. The present study was undertaken to further evaluate the role of PRL on GnRH release. To accomplish this, we set up a static hypothalamic organ culture system which enabled us to evaluate immunoreactive GnRH (iGnRH) release by individually incubated longitudinally halved hypothalami. PRL at the concentrations of 100 and 1,000 nM (2,300 and 23,000 ng/ml) inhibited iGnRH release. This suppressive effect of PRL was apparently specific since growth hormone, a PRL-related molecule, did not have any significant effect on iGnRH release at the concentration of 1,000 nM (21,500 ng/ml) and a PRL antiserum completely suppressed the inhibitory effect of exogenously added PRL. On the other hand, this antiserum had no effect on basal iGnRH release suggesting that hypothalamic PRL does not regulate GnRH release. Based on the observation that PRL exerts a sexually dimorphic effect on plasma gonadotropin levels, we also evaluated the effects of testosterone (T), dihydrotestosterone (DHT), 17β-estradiol (E2), and progesterone (P) on PRL-inhibited iGnRH release in vitro. T, DHT and E2 did not have any detectable effect on PRL-suppressed iGnRH release whereas P, at the concentration of 0.1 nM (0.03 ng/ml), completely abolished the effect of PRL. In conclusion, we report here that PRL inhibits GnRH release by hypothalami explanted from the male rat. Hypothalamic PRL does not seem to have any tonic modulator effect on GnRH release, at least under these experimental conditions. In addition, we found that P is capable of counteracting the effects of PRL on hypothalamic GnRH release. The physiological relevance, if any, of the ‘protective’ effect of this steroid on the hypothalamic GnRH neuron during hyperprolactinemia is not clear at the present

ISSN:0028-3835    

DOI:10.1159/000126355

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The membrane properties of arcuate nucleus (ARN) neurons and their connections with extranuclear regions were examined in vitro, using intracellular recordings obtained in superfused explants of rat hypothalamus. Current-clamp analysis revealed that the electroresponsive properties of a large proportion of ARN neurons are influenced by the expression of various forms of low threshold rectification. When the initial membrane potential of a neuron was maintained negative to –70 mV, depolarizing current injection could precipitate an immediate bursting response, due to the activation of a low-threshold spike, or delay firing as a result of transient outward rectification. These properties represent a means by which changes in membrane potential may modulate the responsiveness of ARN neurons to synaptic input. Indeed, electrical stimulation revealed that in addition to efferent projections to the supraoptic nucleus, medial preoptic area, or neurointermediate pituitary, subgroups of ARN neurons may receive a reciprocal, or collateral innervation from each of these areas. This functional diversity of intrinsic and synaptic mechanisms provides ARN neurons with a high capacity for the complex local processing of afferent informatio

ISSN:0028-3835    

DOI:10.1159/000126356

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Glandular kallikrein (GK) is an estrogen-induced and dopamine-repressed lactotroph protease postulated to play a role in the processing of prolactin (PRL) to novel hormonal forms. Recent studies have shown that GK can process PRL in vitro from a 25K form to a 22K form in the presence of thiols -which appear to transform PRL into conformations (folding states) that are GK substrates. We and others have reported 22K PRL variants in the rat pituitary which can be increased by the administration of cysteamine (CSH), a biological thiol known to alter PRL conformation in vitro and in vivo. The present study further characterized CSH induction of the 22K PRL variant. Estrogen-primed rats were used in dose-response and time-course studies with CSH. CSH effects on 22K PRL levels were studied by Western blot analysis of reduced pituitary extracts (disulfides reduced with dithiothreitol before electrophoresis). Changes in PRL conformation were studied by Western blot analysis of nonreduced samples (thiols and disulfides trapped with iodoacetamide). CSH increased 22K PRL in a dose-dependent manner that was well correlated with the dose-response curve for changes in PRL conformation. CSH at 300 mg/kg produced 10- to 15-fold increases in pituitary levels of 22K PRL. In the time course study, 22K PRL levels peaked within 2 h, plateaued between 2 and 16 h, and approached control levels by 24 h after CSH dosing. CSH-elicited changes in PRL conformation peaked within 1 h, plateaued between 2 and 8 h, and reached control levels within 16 h of CSH dosing. Thus, changes in PRL conformation preceded the changes in 22K PRL levels. CSH actions were not mimicked by bromocriptine, a dopamine agonist that blocks PRL release. CSH-induction of 22K PRL was dependent upon estrogen pretreatment; however, CSH effects on PRL conformation were independent of estrogen treatment. The results support the hypothesis that CSH increases the 22K PRL variant by converting PRL into conformations which are GK substrates.

ISSN:0028-3835    

DOI:10.1159/000126357

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

In ovariectomized (OVX) female guinea pigs sequential administration of estradiol and then progesterone (P) is usually necessary to induce the sexually receptive lordosis posture. Systemic administration of alpha-adrenergic agonists can induce lordosis in OVX guinea pigs primed with estradiol benzoate (EB) alone and facilitate lordosis in OVX females primed with EB and P. In this study, we examined the regional specificity of this regulation by infusing the alpha-adrenergic agonist clonidine (CLON) or the alpha-adrenergic antagonist phentolamine (PHEN) into discrete brain areas. CLON, infused in the medial basal hypothalamus (MBH) of EB-primed females, increased the percentage of females showing lordosis 15–45 min after infusion (p < 0.05) and also increased the number of seconds females held the lordosis posture 15 min to approximately 2.0 h after infusion (by as much as 65% at 15 min p < 0.001). CLON infused in the medial preoptic area (MPOA) of EB primed females had no effect on lordosis except at 4.0 h after infusion when it increased the number of seconds females held the lordosis posture (p < 0.05). In EB + P primed females, PHEN infused into the MBH transiently reduced the number of seconds EB + P primed females held lordosis from 30 min to approximately 2.0 h after infusion (by as much as 64% at 1.0 h; p < O.Ol). Conversely, PHEN infused into the MPOA of EB + P primed females transiently increased the number of seconds females held lordosis from 15 min to 2.0 h after infusion (maximum difference 64%; p < 0.005). These results indicate that alpha-adrenergic receptor mediated signals importantly regulate both stimulatory and inhibitory components of the neuronal network that controls lordosi

ISSN:0028-3835    

DOI:10.1159/000126358

出版商:S. Karger AG    

年代:1993

数据来源: Karger