摘要:

This report concerns ontogenetic aspects of the production and in vitro release of NH2-terminally acetylated forms of melanocyte-stimulating hormone (α-MSH) and β-endorphin by the pars intermedia of the pituitary gland of the mouse. In vitro biosynthetic analysis and radioimmunoassay revealed that approximately 12 h before birth most of the MSH in the fetal pars intermedia is present as des-Nα-acetyl α-MSH. The same non-acetylated peptide is at this stage also the major release form of melanotropin. In 1-day-old mice the level of α-MSH and diacetylated α-MSH had increased considerably, although des-Nα-acetyl α-MSH remained the major form. Five days after birth α-MSH and its diacetylated form constitute the major tissue and release form of the peptide, a situation very similar to that in adult mice. Acetylation of β-endorphin appeared to occur earlier in development, Nα-acetyl β-endorphin (1–31) being the major form of endorphin already in the fetal pars intermedia. It is concluded that in the mouse acetylation of melanotropin and acetylation of β-endorphin are not necessarily concomitant events. It could be established that the ability of the pars intermedia cells for cleaving Nα-acetyl β-endorphin (1–31) to yield C-terminally shortened forms of β-endorphin d

ISSN:0028-3835    

DOI:10.1159/000124524

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

The question as to whether there is lactotroph resistance to dopamine (DA) in pathological hyperprolactinemia (PHP) is unresolved. Previous studies utilizing low-dose DA infusions to study lactotroph function have not considered the diurnal changes in prolactin (PRL) secretion that occur in normals but which are lost in PHP. As PRL levels show a fall in the hours after waking, studies performed during this time of day will falsely show a greater fall of PRL in normals than in PHP patients. The aim was to readdress the issue of lactotroph sensitivity using a study designed to minimize the problem arising from diurnal PRL changes. Eight normal subjects, 17 patients with PHP, and 6 hyperprolactinemic patients with nonfuncitoning pituitary tumors (NFTs) were studied with three graded doses of DA – (0.01, 0.05, and 0.5 µg/kg · min) – by relating the changes induced by each dose to the maximal spontaneous fall in PRL that occurred during a 3-hour control saline study. The mean ±SE maximal fall in PRL during control saline infusion to 46.0 ±4.1% of basal in normal subjects was significantly greater (p < 0.001) than the fall in patients with PHP (88.0 ± 1.0%) or NFTs (87.5 ± 2.6%). The apparent fall in PRL was significantly greater in normals during the two lower infusion doses, but not at the highest dose. When the changes in PRL during each infusion dose were corrected for the nadir achieved during the control saline study, no significant differences were observed at the two lower doses, whilst the 0.5-µg/(kg·min) dose induced a significantly greater (p < 0.05) fall in patients with PHP (26.1 ± 2.0%) and NFTs (22.4 ± 2.0%) than in normal subjects (42.6 ± 6.9%). Plasma DA was significantly higher in the PHP group than in normal subjects during 0.05-(0.93 ± 0.09 vs. 0.58 ±0.05 ng/ml) and 0.5-µg/(kg·min) infusions (5.18 ± 0.54 vs. 3.0 ± 0.22 ng/ml) but not significantly different from the NFT group (0.80 ±0.12 and 4.5 ±0.48 ng/ml, respectively). PRL suppression was negatively correlated with log plasma DA concentration. There was no significant difference in the slopes of the regression lines between the three groups studied. Patients with PHP are as responsive to doses of DA that produced DA levels in the physiological range as normal subjects or patients with NFTs. The diurnal fall of PRL secretion falsely exaggerates the effect of DA in normal subjects. We conclude that the data favor a model of DA deficiency rather than of lactotroph resistance in t

ISSN:0028-3835    

DOI:10.1159/000124525

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

Estrogen induction of cytosolic progestin receptors (CPRs) in the hypothalamus-preoptic area of the female guinea pig is correlated with facilitation of female sexual behavior and gonadotropin secretion by progesterone. The present study validated a CPR microassay and determined where, within microdissected areas of the hypothalamus-preoptic area of the female guinea pig, induction of CPRs by estradiol occurs. Ovariectomized adult guinea pigs were given 20 µg estradiol benzoate (EB) or oil vehicle for 3 successive days. CPRs were measured using the synthetic progestin [3H]-R5020. The highest basal (no estrogen treatment) level of CPRs was seen in the arcuate-median eminence (34.1 ± 3.7 fmol/mg). With EB treatment, the highest level of CPRs was again in the arcuate-median eminence (178.0± 12.0 fmol/mg). EB-treated females also had high CPR levels in the periventricular area (88.5 ± 10.8 fmol/mg) and the medial preoptic area (86.3 ± 9.3 fmol/mg). Moderate levels were seen in the ventromedial nucleus of the hypothalamus (32.7 ± 3.0 fmol/mg) and in the anterior hypothalamic nucleus (13.0 ± 2.1 fmol/mg), but these were not significantly different from the low levels in the medial amygdala (4.5 ± 1.2 fmol/mg) and in the dorsomedial nucleus of the hypothalamus (5.4 ± 1.1 fmol/mg) of EB-treated females. However, EB caused a significant induction over baseline levels not only in the arcuate-median eminence, periventricular area, and medial preoptic area, but also in the ventromedial nucleus of the hypothalamus and the anterior hypothalamic nucleus. EB did not increase CPRs in the medial amygdala or the dorsomedial nucleus of the hypo

ISSN:0028-3835    

DOI:10.1159/000124526

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

Extracellular single-unit activity was recorded from hypothalamic arcuate nucleus (ARC) in brain tissue slices. Adult female Sprague-Dawley rats, ovariectomized or ovariectomized plus estrogen treated for at least 1 week, were used. Resting activity and responses of ARC neurons to six anterior pituitary hormones, or (as a positive control) cholecys-tokinin-octapeptide sulfate (CCK-8S), and a battery of four neurotransmitters including norepinephrine, serotonin, dopamine, and glutamate were recorded. A total of 263 neurons were recorded. Estrogen treatment did not cause any significant changes in the firing patterns nor in responses to most agents tested except for CCK-8S. A large percentage of the ARC neurons were either silent (40%) or slow-firing units (43% fired less than twice/s). Only a small percentage of ARC neurons (20–30%) responded to the anterior pituitary hormones, and these responses were small, delayed increases in firing despite the fact that CCK-8S stimulated more than half of the neurons with large responses. Glutamate was also excitatory, but not quite as effective as CCK-8S. Norepinephrine and serotonin were equally effective in eliciting a neuronal response (over 70% of units responded with an excitation or inhibition). Dopamine acted like norepinephrine, but was less potent. Since anterior pituitary hormones only weakly affected ARC neurons, these electrophysiological data give scant support to the notion that short-loop feedback is accompanied by electrical changes. In the ARC, however, CCK-8S may play some functional roles that are influenced by estroge

ISSN:0028-3835    

DOI:10.1159/000124527

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

The effects of intravenous injection of cupric acetate (CuAc) on release of hypothalamic gonadotropin-releasing hormone (GnRH) and pituitary luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin (PRL) were explored in conscious, ovarian intact does and in ovariectomized (OVEX) does that received subcutaneous implants, either blank Silastic capsules or Silastic capsules containing crystalline estradiol-17β (E2). Animals were subjected to push-pull perfusion of the posterior median eminence for 6 h, and CuAc was intravenously injected (2.5 mg/kg body weight) at the end of the 2nd h of push-pull perfusion. Perfusate samples were collected continuously and pooled for assay at 10-min intervals. Peripheral blood samples were obtained at 10- to 30-min intervals. Levels of GnRH in push-pull perfusate and LH, FSH, and PRL in plasma were measured by specific radioimmunoassays. In intact does (n = 4), intravenous injection of CuAc stimulated the release of hypothalamic GnRH and pituitary LH, FSH, and PRL. The initial increase and subsequent decrease in hypothalamic GnRH after CuAc injection preceded those in plasma LH, FSH, and PRL. Injection of saline into intact does (n = 4) had no effect on any of these hormone levels. In OVEX does that received blank Silastic capsules (n = 4), CuAc failed to stimulate either hypothalamic GnRH release or pituitary LH, FSH, and PRL release. In contrast, CuAc stimulated the release of all four hormones in OVEX does that received E2 containing Silastic capsules (n = 3). These results show that an increase in hypothalamic GnRH release precedes the increase in copper-induced preovulatory gonadotropin release and support the hypothesis that the neuropeptide GnRH mediates this gonadotropin release. The data also are compelling evidence that the action of CuAc requires the presence of the ovaries. One ovarian component in this neuroendocrine process probably is E2

ISSN:0028-3835    

DOI:10.1159/000124528

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

Gonadotrophs of the ovine pars tuberalis have been studied using the patch clamp technique for recording of single ion channel currents. We report that gonadotrophin-releasing hormone (GnRH) acts on these cells to open an inward-current cation channel which is permeable to Ca2+. When measured in cell-attached patches with 5 mM extracellular Ca2+, the GnRH-activated channel has a unit slope conductance of 8.0 ± 2.6 pS (range 4–14 pS). The channel conductance is increased to 13.6 ± 2.4 pS when the external medium contains 95 mM Ba2+ as the charge carrier. GnRH action appears to be mediated through an internal messenger system, since GnRH does not need to be in direct contact with these channels in order to cause their opening. This internal messenger system is unlikely to be Ca2+ itself. In addition, two other voltage-dependent outward-current channels have also been detected, both of which are permeable to K+, but differentiated in the cell-attached recording mode by widely different conductance values of 20–30 and 100–120 pS, respectively, and a reversal potential of –90 to –100 mV. The higher conductance channel is sensitive to internal Ca2+, and its probability of opening is increased in the prese

ISSN:0028-3835    

DOI:10.1159/000124529

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

The cytoarchitecture of the gonadotropin-releasing hormone (GnRH) neuronal system of the female white-footed mouse (Peromyscus leucopus) was characterized using immunocytochemical procedures on thick vibratome sections. Most of the labelled cell bodies are organized loosely into three groups associated with the periventricular region of the medial preoptic area, the diagonal band of Broca, and the olfactory peduncle. A small number of cells are scattered throughout the medial septum, retrochiasmatic area, and in the posterior hypothalamus, lateral from the median eminence (ME). Labelled fibers are distributed widely throughout the brain, with heavy concentrations within the ME and the organum vasculosum of the lamina terminalis (OVLT). A subchiasmatic pathway for GnRH fibers, which courses from the OVLT to the ME, was identified. Fiber plexuses are present in the olfactory bulbs, accessory olfactory bulbs, triangular nucleus of the septum, medial habenular nucleus, and the amygdala. The ependymal layer of the third ventricle that is associated with the ME and OVLT contains large numbers of GnRH fibers, some of which appear to extend into the ventricular lumen. The wide dispersion of the GnRH neuronal system throughout the brain of P. leucopus is evidence that, in addition to its role as a gonadotropin-releasing hormone, GnRH may have a neurophysiologic function in the central nervous system of this species.

ISSN:0028-3835    

DOI:10.1159/000124530

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

Luteinizing hormone-releasing hormone (LHRH) degrading activiy may be of physiological significance as a mechanism capable of partial regulation of hypothalamic LHRH release as well as LHRH levels at the gonadotroph. The possibility of cyclic fluctuations in LHRH-degrading activity was investigated in female rat hypothalami and pituitaries. These tissues were collected at selected time points during the 4-day estrous cycle, homogenized, and centrifuged at 100,000 g. Supernatants were incubated with synthetic LHRH, the reactions terminated, and the decapeptide and its products separated by high-performance liquid chromatography. Degradation of LHRH incubated with active cytosol was estimated by comparison of integrated LHRH peak area with that from incubations with heat-inactivated cytosol. Hypothalamic LHRH degradation was depressed during the latter hours of diestrus 2, a time during which the LHRH content in the hypothalamus has been reported to be increasing. From diestrus 24.00 h to proestrus 15.00 h, there was a significant increase in degrading activity. This was then followed by a decline from 15.00 to 18.00 h proestrus; at the time of the LH surge, the activity had not undergone significant increase in comparison to 18.00 h. Pituitary LHRH degradation was significantly increased during the 6-hour period preceding the surge, but was significantly depressed at the surge. The hypothalamic reduction in activity associated with diestrus 2 as well as the hypothalamic and pituitary reductions associated with proestrus may represent a permissive effect allowing increased LHRH accumulation in the hypothalamus and its prolonged action in the pituitary. These cyclic variations in net LHRH degradation may arise from modulation of one or several peptidases known to degrade the hormone and give further evidence suggesting that the ovulatory cycle may in part be strongly influenced by LHRH-degrading activity.

ISSN:0028-3835    

DOI:10.1159/000124531

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

In order to investigate the physiological role of the brain renin-angiotensin system in the regulation of vasopressin (ADH) release, angiotensin II (Ang II, 10 ng/kg/min) or l-Sar-8-Ile-Ang II (50 ng/kg/min), an Ang II antagonist, was administered intracerebroventricularly to dogs (n = 42) anesthetized with urethane and chloralose after morphine sedation. The effects of the intravenous infusion of either 0.15 M or 2.5 MNaCl (0.1 ml/kg/min, 75 min) were also studied. In control dogs, artificial cerebrospinal fluid (ACSF) was administered at a rate of 10 µl/min for 105 min. ACSF given intracerebroventricularly plus 0.15 M NaCl given intravenously did not affect ADH release, but 2.5 MNaCl given intravenously raised the plasma ADH level in parallel with the rise in plasma osmolality. Heart rate and blood pressure did not change significantly in ACSF along with 0.15 M NaCl, but heart rate increased significantly in ACSF along with 2.5 M NaCl. Ang II along with 0.15 M NaCl significantly raised plasma ADH and decreased heart rate without any changes in blood pressure. Ang II along with 2.5 M NaCl brought about a significant rise in plasma ADH level, arterial blood pressure, heart rate, and plasma osmolality. But simultaneous application of Ang II and 2.5 M NaCl did not result in a larger rise in plasma ADH than that expected from the effects of the two stimulations given separately. Namely, Ang II did not potentiate ADH release elicited by osmotic stimulation. Ang II antagonist given intracerebroventricularly neither affected ADH release and the cardiovascular system in 0.15 M NaCl nor inhibited ADH release in response to osmotic stimulation. Ang II antagonist completely blocked the effects of Ang II. These results clearly show that Ang II given intracerebroventricularly stimulates the receptors within the brain to elicit ADH release, but does not potentiate ADH release provoked by peripheral osmotic stimulation. Ang II does not stimulate the cardiovascular system during 0.15 M NaCl challenge, but stimulates it during 2.5 MNaCl challenge

ISSN:0028-3835    

DOI:10.1159/000124532

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

In an in vitro system, we have demonstrated concomitant release of corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) from the median eminence (ME) of normal and adrenalectomized rats. The ME were incubated in a Krebs-Ringer bicarbonate medium, CRF and AVP released into the medium were measured by radioimmunoassay. The release of both neuropeptides was stimulated by increasing concentrations of potassium (28–56 µM) in the incubation medium, or by addition of veratridine (5–20 µM). In both cases the release process was dependent on the presence of calcium in the incubation medium. Interestingly, potassium-induced release was found to be relatively insensitive to calcium channel antagonists that are potent inhibitors in smooth and cardiac muscle. The sodium channel antagonist, tetrodotoxin (1 µM), completely blocked the effect of veratridine, while no change was seen in the response to potassium. Adrenalectomy increased the ratio of AVP:CRF release from 2:1 in ME removed from sham-operated rats to 8:1 in ME from the adrenalectomized group. We suggest that this ratio of AVP:CRF release may also pertain in vivo, and that AVP could be the predominant corticotropic stimulus in adrenalectomize

ISSN:0028-3835    

DOI:10.1159/000124533

出版商:S. Karger AG    

年代:1986

数据来源: Karger