摘要:

The binding of androgens to specific high-affinity receptor sites in brain tissue is postulated as an initial event in the mechanism of central androgenic action. In an effort to assess the functional capacity of the androgen receptor system in the central nervous system, we measured the concentration of nuclear (ARn) as well as cytosolic androgen receptors (ARc) in 13 microdissected brain samples from intact male and female Sprague-Dawley rats. Tissues from 6 rats were combined for each determination and androgen receptor contents were measured with single-point in vitro assays that used saturating concentrations of high specific activity 3100 fmol/mg DNA) in males were measured in the ventromedial nucleus of the hypothalamus and medial amygdala; intermediate levels (50–100 fmol/mg DNA) were found in arcuate nucleus-median eminence, medial preoptic nucleus, periventricular preoptic area, bed nucleus of the stria terminalis, anterior hypothalamus, periventricular anterior hypothalamus, lateral septum, and parietal cortex, and low levels ( < 50 fmol/mg DNA) were measured in lateral preoptic nucleus and cortical amygdala. With the exception of the periventricular preoptic area (74 ± 33 fmol/mg DNA), only very low concentrations of ARn were measured in females. These data provide the first quantitative profile of ARn in discrete brain nuclei and subregions of the r

ISSN:0028-3835    

DOI:10.1159/000125151

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

A fluorescent immunocytochemical technique was developed to determine if cells in the guinea pig hypothalamus and preoptic area that contain estradiol-induced progestin receptors also contain estrogen receptors. With this technique little or no progestin receptor-immunoreactivity (PR-IR) was observed in the absence of estrogen treatment in ovariectomized guinea pigs. As has been reported previously, priming with estradiol caused a large increase in the concentration of PR-IR cells indiscrete regions of the hypothalamus and preoptic area, primarily in the arcuate nucleus, ventrolateral area of the hypothalamus, periventricular preoptic area, medial preoptic nucleus, medial preoptic area, anterior hypothalamic nucleus and anterior hypothalamus. A range of lightly to intensely labeled estrogen receptor-immunoreactive (ER-IR) cells were observed in high concentration in each of these areas, as well as in some areas in which no PR-IR cells have been identified, such as the amygdala. PR-IR was only observed in cells that also had ER-IR. In some areas such as the ventrolateral hypothalamic area and arcuate nucleus, nearly all medium to highly-fluorescent ER-IR cells also contained estradiol-induced PR-IR, while in the amygdala no PR-IR was observed despite a high concentration of ER-IR cells. These results confirm the hypothesis that progestin receptors are produced in estrogen receptor-containing cells in the brain, and they suggest that these cells are the sites where estradiol and progesterone act to influence behavior and physiology.

ISSN:0028-3835    

DOI:10.1159/000125152

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

The injection of purified α-bungarotoxin (α-BTX), an antagonist of the muscle nicotinic cholinergic receptors, into the third ventricle (3rd V) of ovariectomized rats decreased the frequency of pulses of luteinizing hormone (LH) but had no significant effect on the amplitude or nadir of LH secretion. Approximately 24 h after the 3rd V injection of α-BTX, the pulsatile secretion rate of LH was increased and thus the α-BTX effect was reversible. The 3rd V injection of the two nicotinic cholinergic agents, cytisine (10 µg) and dihydro-β-erythroidine, also decreased the frequency of pulses of LH. Cytisine and dihydro-β-erythroidine inhibited the binding of (125I)α-BTX to rat hypothalamic synaptosomes (P2B) and also to frozen coronal sections of the hypothalamus as studied by film autoradiography. Injection of a lower dose of cytisine (1 µg) had no effect on LH secretion, but when administered with α-BTX into the 3rd V, cytisine significantly reduced the α-BTX-induced decreased LH secretion. The injection of cytisine with (125I)α-BTX into the 3rd V also decreased in vivo labeling of the (125I)α-BTX-binding sites in the hypothalamus of ovariectomized rats. The results suggest that α-BTX can inhibit the pulsatile secretion of LH in ovariectomized rats and this inhibition may be mediated by specific subclass of a CNS (central nervous system) nicotinic acetylcho

ISSN:0028-3835    

DOI:10.1159/000125153

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

The thyroid gland is richly innervated but the effects of activation of these nerves on thyroid hormone secretion are not yet established. In the present study, intravenous injection to mice of 2-deoxy-glucose (2-DG; 60 µmol/animal) was used to activate the autonomic nerves. The nerve activation occurs through the neuroglycopenia. We found that 2-DG inhibited the thyroid-stimulating hormone (TSH; 70 µU/animal)-induced thyroid hormone secretion, measured as release of radioiodine bound to anti-T4 in radioiodine-pretreated mice. This inhibition by 2-DG was completely reversed by the α-adrenoceptor antagonist phentolamine but not affected by the β-adrenoceptor antagonist L-propranolol or the muscarinic receptor antagonist methylatropine. It is therefore concluded that neuroglycopenia-induced activation of the autonomic nerves inhibits TSH-induced thyroid hormone secretion by a mechanism that is reversed by phentolamine. It is suggested that it is mainly the adrenergic nerves that are involved in this action, and, consequently, that the function of the adrenergic nerves in thyroid physiology is to restrain the stimulatory action of

ISSN:0028-3835    

DOI:10.1159/000125154

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

In response to stressors involving tissue injury, pituitary corticotroph secretion of immunoreactive beta-endorphin (iB-END) could be either due to release of hypothalamic factors such as corticotropin-releasing factor (CRF) or to release of a tissue factor from the periphery. In the present experiments, we investigated whether inflamed tissue releases a factor which evokes pituitary secretion of iB-END. In an initial experiment, rats with an inflamed hindpaw due to carrageenan injection had significantly greater levels of circulating iB-END as compared to rats with saline-injected paws. Removal of afferent input, by hindlimb denervation, failed to block the carrageenan-induced increase in iB-END levels. Subcutaneous perfusates were then collected from inflamed and control hindlimbs and applied to rat anterior pituitary cell cultures. Pituitary release of iB-END due to administration of perfusate from inflamed paws was significantly greater than iB-END release due to perfusate from saline-injected paws or to basal release. The releasing activity in the perfusates was blocked in calcium-free medium and was not due to a direct action of carrageenan, bradykinin, substance P or calcitonin gene-related peptide. The results indicate that inflamed tissue releases a CRF-like factor which stimulates iB-END release both in the denervated rat and cultured pituitary cells.

ISSN:0028-3835    

DOI:10.1159/000125155

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

We investigated the effects of metabolites of arachidonic acid on the release of β-endorphin-like immunoreactivity (β-end-IR) from rat anterior pituitary cells. Anterior pituitary cells from female rats cultured with arachidonic acid released β-end-IR in a dose- and time-dependent manner. To determine which metabolites of arachidonic acid stimulated the release of β-end-IR, we examined the effects of an inhibitor of the cyclooxygenase, indomethacin, and an inhibitor of the 5-lipoxygenase, 2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-l,4-benzoquinone (AA-861). β-end-IR release from pitutiary cells induced by arachidonic acid was inhibited about 37% by AA-861 but was not affected by indomethacin. Other lipoxygenase inhibitors (eicosatetraynoic and nordihydroguaiaretic acid) also reduced the release of β-end-IR induced by arachidonic acid. The effects of the 5-lipoxygenase products 5-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE) and leukotrienes (LTA4, B4, C4, and D4) on the release of β-end-IR from rat pitutiary cells were also examined. 5-HETE (1–50 µM) elicited a dose-dependent release of β-end-IR from cultured pitutiary cells, and 50 µM 5-HETE induced β-endorphin release time dependently. LTA4 and LTB4 also significantly stimulated the release of β-end-IR, but LTC4 and LTD4 had no effect. Other lipoxygenase products (12-hydroxy-5,8,10,14-eicosatetraenoic acid, 12-HETE; 15-hydroxy-5,8,10,14-eicosatetraenoic acid, 15-HETE) were also secretagogues at concentrations of above 1 µM. These results suggest that β-end-IR release from rat anterior pituitary cells is stimulated by the 5-lipoxygenase products of arachidonic acid 5-HETE, LTA4 and LTTα and by the other lipoxygenase products 12-

ISSN:0028-3835    

DOI:10.1159/000125156

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

Glucose utilization in rat brain and pituitary was measured in control and water-deprived rats by autoradiographic assessment of the metabolic trapping of radioactivity from [l-14C]glucose. Two days of water deprivation resulted in significant increases in hematocrit, plasma osmolality and vasopressin levels, indicating a functional activation of magnocellular vasopressin neurons. The uptake and retention of radioactivity from [l-l4C]glucose in the dehydrated rats, compared to controls, was 103% greater in the magnocellular portion of the paraventricular nucleus and 74% greater in the supraoptic nucleus. Water deprivation also resulted in significant increases in glucose utilization (30–40%) in the lateral and anterior hypothalamic areas, somatosensory cortex and cingulate cortex. No change in glucose utilization after 2 days of water deprivation was apparent in the parvocellular paraventricular nucleus, periventricular nucleus of the hypothalamus, corpus callosum, organum vasculosum of the lamina terminalis (OVLT) or the subfornical organ (SFO). In the pituitary, glucose utilization was increased in the neural lobe but was unchanged in the anterior and intermediate lobes after water deprivation. Under the conditions of the present study, no increase in metabolic activity was apparent in 2 brain regions thought to be possible sources of osmoreception, the OVLT and SFO. These results do not support, but do not exclude, functional involvement of the OVLT and SFO in regulating the activity of magnocellular neurons of the paraventricular nucleus and supraoptic nucleus during chronic water deprivatio

ISSN:0028-3835    

DOI:10.1159/000125157

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

Aging effects on the hypothalamic-pituitary-adrenocortical system have been studied primarily in the sedentary, environmentally deprived laboratory rat. Since it is known that chronic activation changes the responsiveness of the hypothalamic-pituitary-adrenocortical system, the present experiments were undertaken to determine whether age-related effects on this system would differ between sedentary and chronically stressed rats. Groups of 6- and 20-month-old F-344 rats were exposed to daily sessions of a 2-way shock-escape procedure over a 6-month period. When the rats were 12 (adult) and 26 months of age (old), pituitary-adrenocortical responses to an acute, novel stimulus were examined in young and old chronically stressed and age-matched control rats. Young and old control rats showed essentially the same corticosterone response to an acute motion stress. Chronic stress exposure increased the corticosterone response to the novel acute stressor in young but not in old rats. ACTH levels in response to acute stress were significantly reduced in old control rats compared to young control animals. Chronic stress did not change the ACTH acute stress response in young animals, whereas in old animals chronic stress elevated the ACTH responsiveness so that the old rats showed stress-induced ACTH levels that were comparable to the young animals. In conclusion, the effects of chronic stress on the function of the hypothalamic-pituitary-adrenocortical system are age-dependent, and environmental factors can significantly influence the progression of aging of the hypothalamic-pituitary-adrenal system.

ISSN:0028-3835    

DOI:10.1159/000125158

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

To determine the sites of action whereby estradiol (E2) induces the preovulatory luteinizing hormone (LH) surge in pigs, hypophysial-stalk-transected (HST) ovariectomized (OVX) gilts (mean ± SE: 118 ± 12 kg) received intramuscular injections of E2 benzoate (10 µg E2B/kg body weight) on day 0, plus intravenous pulses of 1 µg gonadotropin-releasing hormone (GnRH) every 45 min either from days -5 to 4, days -5 to 0 or days -5 to 0 then days 2 to 4. A fourth and fifth group received steroid vehicle on day 0 and pulses of GnRH on either days -5 to 4 or days -5 to 0 then days 2 to 4. In stalk-intact OVX gilts, E2B inhibited LH release for 48 h, then induced an LH surge that peaked 60–84 h after steroid treatment. In HST OVX gilts, serum LH increased from undetectable concentrations (<0.17 ng/ml) to 0.42 ± 0.03 ng/ml after 5 days of pulsatile GnRH replacement. In the presence of pulsatile GnRH stimulation, serum LH concentrations were inhibited for 12 h after E2B but then returned to values that were similar to those for HST gilts given GnRH in the absence of steroid treatment. Discontinuing GnRH pulses at the time of E2B injection caused serum LH concentrations to drop to 0.18 ng/ml or less for the remaining 96 h. When GnRH pulses were interrupted for 48 h, beginning immediately after injecting E2B or vehicle to mimic the secretory hiatus of LH and presumably GnRH observed in stalk-intact pigs prior to the surge, resumption of GnRH pulses caused serum LH concentrations to increase progressively over 3 h in E2B-treated gilts but to peak abruptly in controls given vehicle. During this period when GnRH administration was resumed, E2B successively increased LH pulse amplitudes and apparently prolonged the duration of LH release within each pulse, but did not augment the peak serum LH concentration. Before treatments were initiated, serum prolactin concentrations were higher in HST gilts than stalk-intact controls. The transection of the hypophysial stalk did not attenuate the E2B-induced release of prolactin that accompanied the LH surge in stalk-intact gilts. Based on these results, we submit that E2 induces the LH surge in gilts primarily by stimulating GnRH secretion, whereas changes in gonadotrope responsiveness to GnRH may influence only the surge profile. In contrast, E2 acts primarily on the pituitary gland to stimulate prolactin r

ISSN:0028-3835    

DOI:10.1159/000125159

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

The hyt/hyt mouse (BALB/cBY-hyt, C.hytRF) provides a useful model for exploring the effect of inherited severe primary hypothyroidism. Studies were undertaken to try to define the basis of the primary hypothyroidism in mice homozygous for the autosomal recessive gene, hyt. These mice had congenital hypothyroidism of fetal onset after 15 days post conception. Through their lifetime, the hyt/hyt mice had reduced serum thyroxine (T4), triiodothyronine (T3), reduced thyroid gland intralumenal colloid on electron microscopy and a 100-fold elevation of TSH-like activity compared to hyt/+ littermates. Thyroglobulin made in hyt/hyt animals was similar in size to normal thyroglobulin which was inconsistent with a major structural thyroglobulin gene defect. The thyroglobulin was iodinated. Marked, erratic dilation of rough endoplasmic reticulum (RER) was noted in hyt/hyt mouse follicular cells. Despite these ultrastructural findings, pulse chase and immunoprecipitation studies with isolated hyt/hyt and normal thyroid glands indicated that normal thyroglobulin processing occurred in the RER and Golgi of the hyt/hyt mice. The hyt/hyt thyroid glands were hypoplastic compared to hyt/ + littermates. Histologically, the hyt/hyt thyroid glands demonstrated an increase in smaller follicular cells, and greater variability in follicular size compared to hyt/ + littermates. Histological and ultrastructural abnormalities in the gland were similar to those seen in certain cases of human congenital hypothyroidism with TSH receptor insensitivity of the thyroid gland. These findings along with the significant TSH elevation, the reduction in colloid and in serum T3 and T4, the efficacy of the hypothalamo-pituitary-thyroid feedback system, and previous observations of reduced iodine uptake and intrathyroidal T4 [3], suggested that primary hypothyroidism in the hyt/hyt mouse might be due to a defect in TSH responsivity of the thyroid gland.

ISSN:0028-3835    

DOI:10.1159/000125160

出版商:S. Karger AG    

年代:1989

数据来源: Karger