摘要:

Progesterone stimulates prolactin secretion in estrogen-primed women and monkeys. We hypothesize that this effect is neurally mediated since pituitary lactotropes do not contain progestin receptors (PR). In rodents, progesterone enhances hypothalamic serotonin (5HT) content, and both progesterone and 5HT stimulate prolactin and LH secretion. However, it was not known whether progesterone acts directly on 5HT neurons or through other neurons. Using a double immunocytochemical procedure, we show that 5HT neurons in macaque contain PR and thus are a progestin target system. Midbrain tissue blocks were obtained from two female monkeys and immersion-fixed prior to freezing and sectioning. PR was detected with a monoclonal antibody against human PR (B39) bridged to horseradish peroxidase and developed in diaminobenzidine. PR immunoreactivity appeared as a brown reaction product which localized in the nuclei of individual neurons. 5HT was detected with an antiserum generated against a conjugate of 5HT and BSA bridged to alkaline phosphatase. 5HT immunoreactivity appeared as a blue reaction product in the cytoplasm and axons of the pontine raphe nucleus. Neurons containing both nuclear reaction product for PR and cytoplasmic reaction product for 5HT were observed in both the dorsal and ventral aspects of the midbrain raphe nucleus as well as the raphe magnus. In summary, progesterone can have a direct action on 5HT neuronal function and thereby influence those endocrine and affective systems under serotonergic control.

ISSN:0028-3835    

DOI:10.1159/000126334

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Metabolic insults, such as ischemia or hypoglycemia, typically cause severe neuronal injury in the hippocampus and this cell vulnerability can be exacerbated by glucocorticoid (GC) exposure. This endangerment can also be demonstrated in vitro in both neurons and astrocytes. Direct GC effects on cell physiology thus appear to play a role, but the actual mechanism remains unclear. In order to clarify whether GCs act as damaging agents via a ‘classical’ steroid route, we examined the temporal features and steroid-specificity of this synergy in hippocampal astrocyte cultures derived from E18 fetal rats. A 24-hour pretreatment with corticosterone (CORT), the principal GC in the rat, enhanced both hypoxic and hypoglycemic cell damage, as measured by lactate dehydrogenase assay. This damaging effect was abolished when CORT exposure was reduced to 8 or 4 h prior to the hypoglycemic or hypoxic treatment, respectively. A 24-hour exposure to several nonGC steroids also failed to enhance hypoxic cell damage. The damaging effect of CORT was attenuated if steroid exposure occurred during the hypoglycemic insult and was absent in both hypoxic and hypoglycemic paradigms if CORT exposure was limited to the recovery period. These results suggest that GCs aggravate metabolic astrocyte injury via classical hormonal effects that are steroid-specific, receptor-mediated, and emerge slowly after prolonged steroid expos

ISSN:0028-3835    

DOI:10.1159/000126335

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Numerous reports have demonstrated that interleukin-1 β (IL-1β) is a potent secretagogue for adrenocorticotropin (ACTH) and that IL-1α appears to be considerably less efficacious. To clarify apparent differences in the potency of IL- 1α vs. -β on ACTH secretion from a functional perspective, the IL-1 receptor antagonist protein, IRAP, was utilized. Following administration to rats either intravenously (i.v.) or adjacent to the median eminence (intra-ME), IL-1β was approximately 8-fold more potent than IL-1α. IRAP, delivered i.v. or intra-ME, inhibited ACTH secretion due to the administration of IL-1α or -β by the corresponding route. Similar amounts of IRAP were required to attenuate ACTH responses to approximately equieffective i.v. doses of IL-1α (200 ng) or -β (25 ng): IC50 for IRAP inhibition of IL-1α vs. -β was approximately 2.5 or 5.5 µg, respectively. At these IC50 doses, the ratios of IRAP/IL-1 were 12.5 and 220 for IL-1α vs. -β, respectively. These ratios are compatible with mediation by a type I-like IL-1 receptor. To compare these properties of the central IL-1 receptor to a peripheral type I IL-1 receptor in the same species, the IL-1 -enhanced rat thymocyte comitogenesis assay was utilized. Thymocyte proliferation in response to equieffective doses of IL-1α or -β was similarly inhibited by IRAP: approximate IC50 for inhibition of IL-1α vs. -β was 12.5 or 25 ng/ml, respectively. Relative to the dose of IL-1α and -β (5 ng/ml), these amounts of IRAP are within the range required to inhibit (1) the ACTH response to IL-1 in rats, reported herein, and (2) type I IL-1 receptor-mediated responses in peripheral tissues from other species. Thus, the ACTH responses to both IL-1α and IL-1β may be mediated through a central type I-like IL-1 receptor(s), which appears to be similar to the peripheral rat type I receptor. IRAP was effective at inhibiting ACTH secretion stimulated by IL-l when these agents were administered i.v. or into the hypothalamic median eminence, suggesting that type I-like IL-l receptors are present in the median eminence where they are readily accessible to modulat

ISSN:0028-3835    

DOI:10.1159/000126336

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The present work studied the effects of epidermal growth factor (EGF) on the release of thyrotropin (TSH) and prolactin (PRL) from perifused pituitary glands of 200-gram male Wistar rats. Each pituitary gland, cut into halves, was placed in a chamber of a perifusion system connected to a peristaltic pump which conveyed the perifusion medium (Medium 199, pH 7.3, Gibco, USA) from a reservoir to a chamber at a flow rate of 100 µl/min. Each tightly closed chamber contained one pituitary gland and 600 µl medium and it was placed in a water bath at 37 ° C throughout the experiment. One milliliter samples of effluent were collected every 10 min for 60 min to obtain baseline values of TSH and PRL. Thereafter, TSH-releasing hormone (TRH) 10–8M or EGF (10–11, 10–10, 10–9 or 10–8M) were added to individual chambers and the 10-min sampling of effluent continued for 60 min. EGF 10–11M elicited no TSH response, but 10–10 and 10–9M doses induced significant increases in TSH secretion (p < 0.01) with a peak at 10 min after addition of EGF. In another experiment, EGF 10–8M or TRH 10–8M significantly elevated TSH secretion (p < 0.01). However, TRH, but not EGF, stimulated PRL secretion (p < 0.01). In the in vivo studies, the intravenous administration of EGF 10–5 M or TRH 10–5M both induced significant elevation of TSH release at 10 min after the injection (p < 0.02 for EGF and p < 0.01 for TRH). In summary, EGF stimulated TSH secretion from rat pituitary glands in vitro and in vivo, in a magnitude comparable to that

ISSN:0028-3835    

DOI:10.1159/000126337

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Effects of selective γ-aminobutyric acida (GABAa) and GABAb receptor agonists on noradrenaline (NA)-induced and N-methyl-D-aspartate (NMDA)-induced luteinizing-hormone (LH) secretion were examined in ovariectomized estrogen-primed rats. Experiments were performed in unanesthetized animals bearing chronic intracerebroventricular (i.c.v.) cannulae. Lev. injections of NA or NMD A stimulated LH secretion in animals that had received prior i.c.v. injections of saline. The effects of NA and NMDA were significantly attenuated by a prior i.c.v. injection of phentolamine (a selective α-adrenergic-receptor blocker) and 2-amino-5-phosphonovaleric acid (a selective NMDA receptor antagonist), respectively. NA-induced LH release was also inhibited by i.c.v. injections of either muscimol (a selective GABAa receptor agonist) or baclofen (a selective GABAb receptor agonist). On the other hand, although muscimol inhibited the effect of NMDA, baclofen did not inhibit but slightly augmented the NMDA-induced release of LH. These results support the hypothesis that both GABAa and GABAb receptors are involved in the GABAergic inhibition of LH secretion, and further suggest that they are probably located at different sites in the neural mechanism regulating LH secretion in the female ra

ISSN:0028-3835    

DOI:10.1159/000126338

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The anatomical relationship between corticotropin-releasing factor (CRF)- containing cells and arginine vasopressin (AVP)-containing cells in the human hypothalamus was investigated by immunocytochemistry. In the paraventricular nucleus of the hypothalamus (PVH), CRF-like immunoreactivity (CRF-LI) was present exclusively in parvocellular cells, while AVP-like immunoreactivity (AVP-LI) was present in both parvocellular and magnocellular cells. No CRF-immunoreactive neurons were observed in the supraoptic nucleus. All CRF-immunoreactive parvocellular cells in the PVH were also AVP immunoreactive. We confirmed the presence of AVP in the CRF-immunoreactive cells by using two kinds of anti-AVP antisera, one of which recognized the side chain of AVP while the other recognized the ring structure of AVP. Colocalization of CRF-LI and AVP-LI was observed not only in the same perikarya but also in the same nerve fibers of parvocellular cells. The present results raise the possibility that AVP and CRF may be secreted together into the human portal circulation.

ISSN:0028-3835    

DOI:10.1159/000126339

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The effect of central administration of bombesin (BB), a neuropeptide originally isolated from the skin of frogs, on the estrogen-induced afternoon prolactin (PRL) surge was studied. Two doses of BB, 0.15 and 0.75 µg/rat, were injected into the lateral cerebroventricle of estrogen-primed ovariectomized rats at 12.00 h through preimplanted cannulae. Serial blood samples were obtained through preimplanted intra-atrial catheters during the whole afternoon hours. The small dose of BB delayed the afternoon PRL surge for an hour, but did not prevent it from occurring. The large dose of BB, however, blocked the surge completely. When the same effective dose of BB was co-administered with a BB antagonist, [Leu13-ψ(CH2NH) Leu14]-BB (LψL-BB), it no longer inhibited the PRL surge. The afternoon PRL surge was also reinstated in BB-treated rats by giving a single injection of sulpiride (1 µg/rat, i.v.), a dopamine antagonist, at 14.00 h in the same afternoon. These results suggest that BB, by acting through specific BB receptors, can inhibit the PRL surge possibly through activating the dopaminergic syst

ISSN:0028-3835    

DOI:10.1159/000126340

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Some physiological parameters of pineal 5α-dihydrotestosterone receptor in the rat such as ontogeny, circadian rhythm pattern, and its modulation by various neuropeptides and neurotransmitters which have profound influences on the pineal hormone melatonin were examined. Pineal 5α-dihydrotestosterone receptors measured at different ages of the animal revealed that on day 10 both cytosolic receptor (CR) and nuclear receptor (NR) levels were high. With growth and development both groups of receptors declined and during puberty started again to rise. During adulthood both receptors were high; however, NR rose further with full maturation. Both groups of receptors showed circadian rhythmicity. While the CR was significantly higher at 6.00 h than at any time point through 24 h, the NR peaked at 18.00 h when the difference between both groups was maximum. Castration caused significant increment of NR. Treatment of castrated animals with a low dose of testosterone propionate (0.25 mg) significantly stimulated both receptor groups, while treatment with a high dose (2.5 mg) failed to do so. Treatment with various substances such as antiandrogen, opioids, neuropeptides, and neurotransmitters significantly modulated the pineal androgen receptor population: cyproterone acetate and monosodium glutamate suppressed CR; growth hormone releasing hormone increased NR; growth hormone release inhibiting hormone had no significant effects on either group of receptors; exogenous melatonin and norepinephrine increased NR; β-endorphin increased only NR, but methionine enkephalin stimulated both, and epithalamine had no significant effects on either group of receptors, but thymosin α1 increased NR. The results from the current study demonstrate that while all the substances tested can significantly alter the biosynthesis of pineal melatonin, some had augmentary or inhibitory effects on either group of receptors, and there is no corresponding parallel pattern between melatonin and androgen receptors. It is possible that the effects seen in the current study are not mediated through melatonin biosynthesis, but by some other pineal fact

ISSN:0028-3835    

DOI:10.1159/000126341

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Cocaine (COC) has been described as exerting potent stimulatory effects on the hypothalamo-pituitary-adrenocortical (HPA) axis. In the present study, we investigated the acute and chronic effects of intracerebroventricular and intrahypothalamic injections of COC in rats. Twenty minutes following intracerebroventricular injection of COC (1-100 µg), dose-dependent increases in plasma corticosterone (CS) were observed, although the highest dose tested (100 µg) evoked a significantly smaller response than that following 50 µg. Prior stressing of the animals resulted in elevated plasma CS levels (315 ± 16 ng/ml) and significantly decreased plasma CS concentrations following 50 µg COC (87.8 ± 3.2%). Injections above the hypothalamic paraventricular nucleus (PVN), the site of corticotropin-releasing-factor-secreting neurons which regulate HPA activity, required relatively higher doses of COC in order to elicit increases in plasma CS; injections of 0.5 µg had no effect, 1 µg resulted in an increase to 168 ± 68 ng/ml (p < 0.005), and 2.5 µg produced an increase to 146 ± 29 ng/ml (p < 0.025). Post-PVN injections of COC, behind the posterior margin of the PVN in the vicinity of the ventral noradrenergic ascending bundle, also required a high dose (2.5 µg) in order to elicit a plasma CS response (208 ± 19 ng/ml; p < 0.005), with no significant response seen following 0.5 µg COC. No effects of specific neurotoxic lesions of the catecholaminergic or serotonergic innervation of the hypothalamus were observed upon adrenocortical responses to COC. Chronic intracerebroventricular administration of COC (5 µg/day, 10 days) to conscious rats resulted in significant elevations in basal plasma CS (238 ± 36 ng/ml; p < 0.025) above that found in saline-treated animals (129 ± 19 ng/ ml). However, animals receiving daily COC injections were able to exhibit a similar CS response (336 ± 26 ng/ml) to that seen in the chronic saline-treated group given an acute intracerebroventricular COC challenge (328 ± 23 ng/ml). Neurochemical changes in monoamine metabolism were also measured in medial prefrontal cortex, hippocampus, and hypothalamus following single or repeated daily injections of COC, and these are discussed in the context of the data on adrenocortical responses. The results of this study demonstrate that while a local intrahypothalamic action of COC may elicit HPA activation, probably through a stimulation of catecholaminergic activity, the predominant site of action of COC in such activation appears to reside elsewhere in the central nervous system. The elevated plasma CS concentrations observed even in saline-challenged rats following chronic COC administration may reflect an anxiety state similar to that seen in chronic human COC users. At the same time, however, these changes do not appear to alter the responsiveness of the HPA axis to subsequent

ISSN:0028-3835    

DOI:10.1159/000126342

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The growth hormone releasing factor (GRF) stimulated adenylate cyclase activity was evaluated in membrane fractions of anterior pituitary glands from male and female rats and in gonadectomized rats following in vivo gonadal steroid treatments. The baseline adenylate cyclase activity was lower in random estrous cycle female rats as compared with males. When estrous cycle phases were evaluated, diestrus 1 females had a lower basal activity as compared with males, while proestrus females were similar to males. The maximal stimulation of adenylate cyclase activity by GRF (i.e. Vmax) was lower in random estrous cycle female rats than in males. This lower Vmax, relative to males, was more pronounced in diestrus 1 than in proestrus females. There was little difference in the ED50 for GRF-stimulated adenylate cyclase activity among these groups. The adenylate cyclase activity was altered 1 week after gonadectomy or 1 week after gonadectomy plus simultaneous in vivo gonadal steroid treatment. The expression of data as a function of whole tissue (content) or as a function of protein (concentration) influenced magnitude and direction of these treatment effects. This may reflect the proliferation of nonsomatotroph cell populations and altered protein synthetic activity following reproductive endocrine manipulations. When expressed as a whole tissue content, the baseline adenylate cyclase activity was unchanged after gonadectomy when compared to same-sex, gonadal-intact cohorts. However, an increase in the Vmax for GRF-stimulated adenylate cyclase activity was found in gonadectomized rats relative to sham-operated, gonadal-intact cohorts. When the same data were calculated relative to protein concentration, a decrease in baseline was found following orchidectomy, but not following ovariectomy, when compared to sham-operated, gonadal-intact cohorts. The corresponding Vmaχ for these groups, expressed as a concentration, decreased after orchidectomy, but increased after ovariectomy. Gonadectomy plus estrogen treatment decreased both baseline and Vmax for GRF-stimulated adenylate cyclase activity. This potent decrease was evident when compared to either same-sex, gonadectomized, or gonadal-intact cohorts for both forms of data expression. Basal and maximally stimulated adenylate cyclase activities following ovariectomy plus testosterone treatment were similar to gonadal-intact females when the data were expressed as a content, but similar to ovariectomized rats when the same data were expressed as a concentration. None of the above treatments significantly altered the ED50 for GRF-stimulated adenylate cyclase activity. These data indicate sex differences for in vitro basal and GRF-stimulated adenylate cyclase activity in rat anterior pituitary membranes. With heterotypic in vivo steroid treatment, estrogen was inhibitory, while testosterone partially was stimulatory to basal and GRF-stimulated adenylate cyclase activity

ISSN:0028-3835    

DOI:10.1159/000126343

出版商:S. Karger AG    

年代:1993

数据来源: Karger