摘要:

The activities of incertohypothalamic (IH) and tuberoinfundibular (TI) dopamine (DA) neurons were compared in selected brain regions of male and female rats by measuring the rate of DA turnover (α-methyltyrosine-induced decline in brain DA concentrations). The rates of DA turnover in regions containing TIDA (median eminence) and rostral IHDA (rostral periventricular and medial preoptic nuclei) neurons were greater in diestrous females than in intact males. In contrast, the rate of DA turnover in the caudal IHDA neurons (medial zona incerta), was greater in intact males than diestrous females. These results indicate that the activities of IHDA neurons, like those of TIDA neurons, differ between the sexes but that the sexual differentiation of IHDA neurons is not homogeneous. Two weeks following orchidectomy, the rates of DA turnover were increased in the median eminence and decreased in the medial preoptic nucleus. Testosterone replacement in orchidectomized males produced opposite effects, causing a decrease in DA turnover in the median eminence and an increase in the medial preoptic nucleus. In female rats, the rates of DA turnover were decreased in the median eminence and medial zona incerta and increased in the medial preoptic nucleus 2 weeks following ovariectomy. Only in the median eminence did 2 days of estrogen replacement in ovariectomized rats produce effects opposite those seen after ovariectomy alone. These data show that the activities of IHDA neurons, as estimated from measurements of DA turnover, can be altered by the removal and replacement of the gonadal steroids

ISSN:0028-3835    

DOI:10.1159/000124656

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

We have previously shown that chelated copper stimulates LHRH release from explants of the median eminence area (MEA). Characteristics of this release process are: ligand and metal specificity, the involvement of a limited number of copper interactive sites, and a lack of dependence on extracellular calcium. Since chloride transport is essential for exocytosis of peptides and biogenic amines, we wished to ascertain if chloride transport is essential for the process of CuHis-stimulated release of LHRH. MEA explants were incubated for 15 min with 100 µM CuHis (phase I) and then for 15 min in copper-free medium (phase II) and LHRH released into the medium was evaluated by RIA. In the presence of 136 mM Cl, CuHis stimulated the release of LHRH from a basal level of 5±0.4pg/15 min per MEA to 17 + 0.9 pg during phase I and to 30 ± 1.2 pg during phase II. In the absence of Cl∼, the CuHis-stimulated release of LHRH during phases I and II was inhibited by 80 and 90%, respectively. In the presence of 136 mMCL and the anion transport inhibitor SITS (4-acetamido-4’-isothiocyanostilbene-2, 2’-disulfonic acid) the stimulated release was completely inhibited in both phases. When the selectivity of this release process for monovalent anions was tested, the effectiveness of the anions in supporting CuHis-stimulated LHRH release was in this decreasing order: Cl– Br– SCN– I– = isethionate. In addition, we noted that CuHis-stimulated release was a saturable function of [CL]; the saturating [Cl–] for phase I was about 40 mM and the shape of the curve was hyperbolic; the saturating [Cl–] for phase II was about 100 mM and the curve was sigmoid. These results indicate that the process of CuHis-stimulated release of LHRH (1) is dependent on chloride transport, (2) exhibits a selectivity for monovalent anions and (3) involves a limited number of CL transport sites. The hyperbolic and sigmoid shapes of the [CL] curves are consistent with a single population of Cl– transport sites involved in LHRH release during the exposure to CuHis and with multiple populations after the exposure to CuHis. We propose that the process of CuHis-stimulated release of LHRHoperates by compound exocytosis in which an influx of chloride leads to LHRH release

ISSN:0028-3835    

DOI:10.1159/000124657

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

Copper, complexed to histidine (CuHis), stimulates LHRH release from explants of the median eminence area (MEA). To gain further understanding of the mechanism of copper action, in this study, we assessed the Na+ and energy requirements for CuHis stimulation of LHRH release. MEA explants, obtained from adult male rats, were incubated at 37 °C for 15 min with 100 µM CuHis and then for 45 min in CuHis-free medium (Krebs-Ringer-phosphate buffer, pH 7.4). LHRH released into the medium was evaluated by RIA. When the incubation buffer contained 143 mM Na+, CuHis stimulated the release of LHRH from a basal level of 17.2 ± 1.26 (mean ± SEM, n = 7) to 74.5 ±6.2 pg/60 min per MEA. When [Na+] was reduced to 16 mM Na+ (by substituting with Li+), CuHis-stimulated LHRH release was inhibited by 80% (p< 0.001); indicating a requirement for Na+. In addition, we found that CuHis-stimulated LHRH release was a saturable function of Na+ concentration; saturation achieved with about 100 mM Na+. To assess the requirement for Na+ transport, we evaluated the effect of 1 mM ouabain, 10 µMtetrodotoxin (TTX), or 100 µM amiloride on CuHis stimulation of LHRH release. Ouabain inhibited CuHis stimulation of LHRH release by 80%, whereas TTX and amiloride were ineffective. In addition, we observed that CuHis did not stimulate LHRH release when incubation was carried out at 4 °C or at 37 °C in the presence of 5 mM KCN. In summary, these results indicate that the process of CuHis-stimulated release of LHRH from the median eminence has a requirement for extracellular Na+, for thermic and metabolic energy, for the activity of the enzyme Na+/K+ ATPase, and for Na+ transport by a limited number of sites. These requirements are supportive of the proposition that CuHis is taken up by the LHRH axonal terminal by co-transport with Na+, the driving force of which is the Na+ electrochemical gradient generated by NaVK+

ISSN:0028-3835    

DOI:10.1159/000124658

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

Pieces of intact or degenerated sciatic nerves autografted into contact with transected neurosecretory axons within the hypothalamus were invaded by neurophysin-positive axons. With increasing time after grafting, increasing numbers of axons were present in both types of grafts, but grafts of degenerated sciatic nerves always contained more axons. At the fine-structural level typical neurosecretory as well as nonneurosecretory axons were usually associated with basal lamina-enclosed neurolemmocyte processes; occasional axons occurred among collagen fibrils or within basal lamina scaffolds. Profiles with the fine structural characteristics of axon terminals were present by 20 days after transplantation.

ISSN:0028-3835    

DOI:10.1159/000124659

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

Experiments were conducted to determine when during perinatal development testicular steroids act in ferrets to promote the organization of a bilateral nucleus in a medial position at the border of the preoptic area (POA) and anterior hypothalamus (AH), henceforth referred to as the male nucleus of the POA/AH (MN-POA/AH). The formation of the MN-POA/AH was promoted in female offspring by treating their mothers with testosterone over the last 11 days of the 42-day gestation period, whereas MN-POA/AH formation was not disrupted in males castrated within 1, 2 or 5 days of birth. Additional experiments were conducted to determine whether the active hormone which induces differentiation of the MN-POA/AH in the male ferret is an androgen or an estrogen. MN-POA/AH formation was inhibited in males deprived prenatally of estrogenic stimulation via maternal ovariectomy and subcutaneous implantation of the aromatase inhibitor l,4,6-androstatriene-3,17-dione (ATD) on gestational day 30. By contrast, MN-POA/AH formation was not disrupted in males exposed prenatally to the antiandrogen flutamide. These results imply that estrogen, derived from the neural aromatization of circulating testosterone, acts prenatally to promote the organization of the MN-POA/AH in male ferrets. The development of sex-dependent features of forebrain morphology may depend on the neural action of estrogen in males of diverse mammalian species.

ISSN:0028-3835    

DOI:10.1159/000124660

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

To determine if oxytocin (OT) may have a modulatory role on corticotropin-releasing factor (CRF) and vasopressin (AVP) mediated ACTH-cortisol release in women, serial experiments were performed in which saline, OT, AVP and CRF were administered singly or in combinations. OT administration (2 IU intravenous bolus followed by 111 mlU/min infusion for 3 h) maintained a circulating concentration of 7.7 × 10"8 Mand did not significantly influence basal, AVP or CRF-induced ACTH-cortisol release. In contrast, OT inhibited significantly the potentiating effect of AVP on CRF-stimulated ACTH-cortisol release. These findings suggest that OT and AVP may modulate, in a reciprocal fashion, the CRF-mediated ACTH release and support the contention that OT may be involved in the neuroendocrine response to stress in women

ISSN:0028-3835    

DOI:10.1159/000124661

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

The in vitro release of LHRH from hypothalami of adult male rats (intact, 5-day castrates, 5-day castrates replaced with various doses of testosterone) was measured under basal conditions and after the addition of KC1, the opiate antagonist naloxone or the opiate agonist DAGO to the perifusion medium. Hypothalami from all treatment groups responded to 56 mM KCl with an increased output of LHRH. LHRH release was also induced by naloxone (10–6M), but only from tissues derived from intacts and castrates given physiological doses of testosterone. The opiate agonist DAGO (10–6M) did not alter the basal release of LHRH; it, however, caused a significant decrease in the K+-induced release of LHRH from hypothalami derived from intact rats and rats replaced with physiological levels of testosterone but not from those derived from castrate rats or castrate rats replaced with small amounts of testosterone. The specificity of this latter response was shown by its reversibility with naloxone. The lack of DAGO effects upon tissues from rats with low levels of steroid implied steroid dependency of the response to opioidergic influences and indeed, the response to DAGO was restored when testosterone was replaced at physiological doses. Measurement of hypothalamic LHRH content showed no significant differences between tissues obtained from intact, castrate and testosterone-replaced castrate rats. These in vitro data support the view that the inhibitory influence of opioids upon LHRH release depends on the presence of gonadal steroids in v

ISSN:0028-3835    

DOI:10.1159/000124662

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

Evidence that γ-aminobutyric acid (GABA) and benzodiazepine receptors play a role in the inhibition of ACTH-cortisol secretion in humans has until now been drawn only from data indicating that sodium valproate, a GABA mimetic, and diazepam, a benzodiazepine, decrease hypothalamus-pituitary-adrenal (HPA) axis secretion in patients affected by pathological hypersecretion of the axis. Therefore, the present study investigated the effects, in the same healthy subjects, of sodium valproate or diazepam, on both basal and stress-stimulated concentrations of β-endorphin (β-EP), β-lipotropin (β-LPH) and cortisol. A single maximal dose of sodium valproate (400 mg) or diazepam (10 mg) did not significantly modify basal concentrations of β-EP, β-LPH and cortisol. On the other hand, in the same subjects, pretreatment with sodium valproate (20 mg × 3) or diazepam (10 mg × 2) blocked the increases in these hormones produced by hypoglycemic stress in all patients tested (p< 0.01 vs. placebo at 45, 60 and 90 min after insulin injection), without affecting the decrease in blood glucose levels. The present data show that sodium valproate and diazepam inhibit stress-induced β-EP, β-LPH and cortisol secretion in humans, suggesting that endogenous GABA and benzodiazepine receptors participate in physiological mechanisms regulating the activity of th

ISSN:0028-3835    

DOI:10.1159/000124663

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

Pharmacological doses of gonadotropin-releasing hormone (GnRH) are known to induce prolactin (PRL) release in different pathological states. The same effect can be observed in postmenopausal women and during the phases of menstrual cycle characterized by high estrogen levels. With the aim to evaluate whether nonpharmacological doses of GnRH are also able to induce PRL release, gonadotropin and PRL response to a low dose of GnRH (10 µg, i.v. bolus) was evaluated in 70 normal women during different phases of their menstrual cycle. A significant PRL increase was observed in 33% of subjects during the first days of the cycle (menstrual phase; days 1–3 from the beginning of menstrual bleeding; n = 6), in 24% of subjects during early follicular phase (days – 10 to -8 from LH peak; n= 17); in 38% of subjects during midfollicular phase (days – 6 to – 4 from LH peak; n = 8); in 78% of subjects during preovulatory phase (days – 2 to – 1 from LH peak; n = 9); in 67% of subjects during postovulatory phase (days + 1 to +2 from LH peak; n = 6) and in 42% of subjects during midluteal phase (days +5 to +8 from LH peak; n = 24). In brief, the increase of mean PRL levels after GnRH administration was only significant (p < 0.05) during pre- and postovulatory phases. The percentage of patients who showed a PRL response during the different phases of menstrual cycle was significantly correlated to the mean maximal net increase of LH (r = 0.927; p < 0.01) and to the mean maximal net increase of FSH (r = 0.926; p < 0.01). In conclusion, the present data show that in normal cycling women the administration of exogenous GnRH induces PRL release even at low doses. The PRL-releasing effect of GnRH is variable throughout the menstrual cycle and it is maximal during the periovulatory period. The significant correlation between PRL release and gonadotrophs responsiveness to GnRH suggests that a paracrine interaction between gonadotrophs and lactotrophs might exist al

ISSN:0028-3835    

DOI:10.1159/000124664

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

The purpose of this study was to determine the role of endogenous opioid peptides in the differentiation of the neuroendocrine brain that leads to estradiol-dependent LH release in female but not in male rats. Newborn intact or gonadectomized rats were given an opiate antagonist, naltrexone, with or without an opiate agonist, morphine, or saline alone during the critical period of the sexual differentiation of the brain (days 1–10). These animals were weaned on day 21 and injected with estradiol benzoate (EB) in oil or oil alone twice, 48 h apart, and the action of EB on plasma and pituitary levels of LH was studied. The release of LH during the prepubertal period was increased following EB treatment both in intact females and gonadectomized males and females, but not in intact male rats. Naltrexone treatment during the neonatal period prevented the EB-induced LH release in both intact and gonadectomized rats. Morphine blocked the inhibitory effect of naltrexone on LH release. Naltrexone treatment did not directly affect pituitary LH storage, but prevented EB-induced depletion of pituitary LH pools; morphine blocked this action of naltrexone. Hence, the inhibitory effect of naltrexone on LH release appeared to result from an alteration of the central mechanism responsible for EB-induced LH secretion. These results suggest a possible involvement of endogenous opioid peptides in the neuroendocrine brain differentiation that results in LH release after EB treatment during the prepubertal period in rat

ISSN:0028-3835    

DOI:10.1159/000124665

出版商:S. Karger AG    

年代:1986

数据来源: Karger