摘要:

The mechanism of cimetidine-induced prolactin (PRL) release was studied. Intracarotid (i.a.) administration of 1 mg/kg of impromidine, the most specific H2 histamine agonist known, did not counteract the cimetidine-induced hypersecretion of PRL. Pre-treatment with benzodiazepines (diazepam or lorazepam, 3 mg/kg/i.a.) completely suppressed it. Administration of γ-aminobutyric acid (GABA 5 mg/kg/i.a.) was also able to prevent it, but to a lesser extent than benzodiazepines. Simultaneous administration of doses of diazepam (1.5 mg/kg/i.a.) and GABA (3 mg/kg/i.a.) ineffective per se markedly blunted the increase of PRL by cimetidine. We conclude that cimetidine does not induce hypersecretion of PRL by its action on histamine H2 receptors, but through other pharmacological activities of the drug, such as perhaps interaction with the GABA-ergic system in the pituitary

ISSN:0028-3835    

DOI:10.1159/000124073

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

We describe a push-pull perfusion technique to investigate the role of somatostatin in the pharmacological suppression of growth hormone (GH) secretion. Immunoreactive somatostatin (IRS) released from the median eminence (ME) was studied in chronically cannulated, unanesthetized male rats. In control rats which received vehicle injection, plasma GH levels showed a normal ultradian rhythm and relatively stable levels of IRS (around 30 pg/15 min) appeared in the perfusate during the 6-h perfusion. Intracerebroventricular (i.c.v) administration of human growth hormone (40 µg), neurotensin (2 µg), glucagon (25 µg) or intravenous (i.v.) injection of oxymetazoline (50 µg/kg b.w.), an α-adrenergic agonist, or endotoxin (150 µg/kg b.w.) suppressed subsequent GH surges. In these rats, however, IRS levels in the ME perfusate failed to change significantly compared to control rats. These results suggest that changes in somatostatin release may play a minor role in the suppression of plasma GH levels caused by these substances, and that major regulatory effects may be achieved via the suppression of growth hormone-releasing factor re

ISSN:0028-3835    

DOI:10.1159/000124074

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

The observation that suckling evokes a modest rise in serum TSH when compared with that of prolactin is inconsistent with the hypothesis that TRH serves as a hypophysiotropic mediator of this response. In the present study we attempted to provide an explanation for this discrepancy by determining whether any of a growing number of putative prolactin releasing factors could alter pituitary responsiveness to TRH. Anterior pituitaries from lactating (day 14) rats were monodispersed with trypsin, cultured for 2 days, and then incubated in the presence of medium alone or medium containing TRH, dopamine, or a combination of these secretagogues. Companion sets of cultures were incubated concurrently with either β-endorphin, neurotensin, oxytocin, serotonin, vasoactive intestinal polypeptide, or lysine vasopressin. As expected, TRH stimulated and dopamine suppressed prolactin release. None of the substances tested except oxytocin had a significant effect on pituitary cell responsiveness to TRH or dopamine. Oxytocin had no effect on prolactin secretion when tested alone or in combination with TRH and dopamine. TRH alone stimulated TSH release by these cultures, while oxytocin and dopamine were ineffective by themselves. However, TSH secretion by cultures treated simultaneously with TRH and oxytocin could be suppressed to approximately half of that released by cells incubated with TRH alone. These results demonstrate that oxytocin attenuates TRH-induced TSH release by a direct action on pituitary cells without affecting the prolactin response. This selectivity of responsiveness imparted by oxytocin might contribute to the blunted release of TSH after suckling

ISSN:0028-3835    

DOI:10.1159/000124075

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

The threshold of light irradiance capable of inhibiting nighttime pineal serotonin N-acetyltransferase (NAT) activity and melatonin content, and the importance of intact photoreceptors and eye pigmentation on these changes, were investigated in the rat. Groups of intact albino and black-eyed rats and albino animals with light-induced photoreceptor damage were studied in the dark period before, and after 15 and 30 min of exposure to either 0.0005, 0.175 or 3.33 µW/cm2 irradiance of light. In animals with photoreceptor damage, the sensitivity of the pineal gland to light decreased so that only the highest irradiance tested (3.33 µW/cm2) was capable of totally inhibiting pineal NAT activity and melatonin levels. In one study, pineal NAT and melatonin levels in intact albino rats were inhibited by all three irradiances studied. In a second experiment, albino and black-eyed animals behaved identically, only responding with a depression in pineal NAT and melatonin after exposure to light irradiances of either 0.175 or 3.33 µW/cm2. In conclusion, the lowest irradiance of cool white light capable of inhibiting pineal NAT and melatonin in albino rats is around 0.0005 µW/cm2. At the irradiances studied, photoreceptor damage influences the response of pineal NAT and melatonin to acute light exposure at night. On the other hand, eye pigmentation does not seem to have a major effect on the nighttime inhibition of the pineal by li

ISSN:0028-3835    

DOI:10.1159/000124076

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

The effects of intraventricular infusions of artificial cerebrospinal fluid (aCSF) or angiotensin II (AII) on LH secretion were investigated in rats that had been ovariectomized for 8 days. In untreated ovariectomized rats, the mean whole blood concentration of LH as well as the amplitude, frequency, and nadir of the LH pulses were not affected by infusion of aCSF or 15 ng AII/h, but were suppressed in a dose-dependent fashion by infusion of AII at doses of 150 or 600 ng/h. The AH receptor antagonist, saralasin, blocked the inhibitory effect of AII, demonstrating the specificity of the response to AII In ovariectomized rats pretreated with estradiol, infusion of AII did not modify mean blood LH levels. However, in ovariectomized rats pretreated with both estradiol and progesterone, infusions of AII at 150 or 600 ng/h produced dose-dependent increases in mean LH concentrations. The results demonstrate both inhibitory and stimulatory effects of AII upon LH secretion, the direction of the effect being determined by gonadal steroids.

ISSN:0028-3835    

DOI:10.1159/000124077

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

Hypothalami, anterior pituitary gland segments and adrenal glands were removed from female Wistar-derived rats decapitated at various times of the day. Blood and tissue hormone concentrations were measured and the tissues challenged with appropriate stimuli in vitro. Both bioactive and immunoreactive corticotrophin-releasing factor (CRF) content of the hypothalami were significantly higher in the evening than in the morning, as was the basal release of bioactive CRF in vitro. The response of the hypothalami to serotonin or acetylcholine added in vitro did not change with time of day. Basal bioactive and immunoreactive adrenocorticotrophin (ACTH) release from the anterior pituitary gland was significantly increased in the evening, as was the response to synthetic ovine CRF in vitro. Plasma ACTH concentrations in intact rats given crude CRF (hypothalamic extract) in vivo were higher in the evening at all times after injection tested, but this difference was markedly reduced in animals with mediobasal hypothalamic lesions. Corticosterone released basally from adrenal glands in vitro was significantly increased in the evening and the response to added ACTH 1–24 was slightly enhanced. For adrenal glands removed from lesioned rats, the pattern was reversed, corticosterone release in vitro being lower in the evening for all doses of ACTH added. Similarly in vivo, in intact rats given ACTH 1–24, plasma corticosterone concentrations and corticosterone release in vitro from adrenal glands removed after the injection were higher in the evening. After the placement of basal hypothalamic lesions, the situation was reversed, the response to ACTH administration in vivo being greater in the morning. The peaks in plasma concentrations of ACTH and corticosterone occurred 1 h later than the peak in hypothalamic CRF release. Therefore, it appears that the timing of the diurnal variation in plasma levels is dictated by the hypothalamus, but circadian changes in the output and responsiveness of the pituitary gland to CRF and the adrenal glands to ACTH play a major role in determining the amplitude of the rhy

ISSN:0028-3835    

DOI:10.1159/000124078

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

We have examined the spinal cord for the presence of glucocorticoid-binding sites. For this purpose, cytosol from the spinal cord of adrenalectomized rats was incubated with (3H)-dexamethasone. Maximal binding was obtained after 20 h of incubation at 0 °C in the presence of 20 mM molybdate, whereas at 20 °C the maximum was at 2 h. Using a range of (·Η)-dexamethasone concentrations (0.2–30 nM), low capacity (161 ± 23 fmol/mg protein) and high affinity (Kd 3.2 ± 0.3 nM) sites were measured. Binding sites decreased by 25% and Kd increased 2.5-fold after incubation with a pure glucocorticoid (RU 26988). Relative binding affinities of several competitors of 10 nM(3H)-dexamethasone were: triamcinolone acetonide 108, dexamethasone 100, RU 26988 54, corticosterone 18, progesterone 17, aldosterone 7, estradiol and testosterone <1. Sedimentation coefficients in glycerol gradients containing molybdate were in the range of those published for glucocorticoid receptors (9.6–9.8 S). Binding of (3H)-dexamethasone was decreased by omitting a SH-protective agent from the buffer or by addition of SH-blocking reagents such as N-ethylmaleimide and p-chloromercuribenzoate. Using rats of different ages, it was found that binding sites were much lower in spinal cord from 2- to 8-day-old rats than in rats of 13–20 days and adults. Regional distribution studies using cytosol from spinal cords dissected between vertebrae C1–C2, C3–C7, T1–T8, T9–L3 and L4–L6 revealed that binding sites were higher in regions containing the cervical (C3-C7) and lumbar (T9-L3) enlargements, with respect to L4–L6. These studies suggested that the spinal cord contains cytosolic-binding sites resembling glucocorticoid receptors, and that the reported action of these steroids on spinal cord function could be

ISSN:0028-3835    

DOI:10.1159/000124134

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

The medial preoptic area (MPOA) and the dorsomedial-ventromedial nuclei (DMN-VMN) of the hypothalamus regulate the mating-induced nocturnal and diurnal surges of prolactin in rats. The neural mechanisms governing the release of the two surges differ. For the nocturnal surge the MPOA serves an inhibitory role while the DMN-VMN serves a stimulatory role. The diurnal surge is controlled by both areas functioning as stimulatory centers. The goal of the present study was to explore the possibility of functional interactions between the MPOA and the DMN-VMN in control of mating-induced prolactin secretion. Stimulation of the MPOA in conscious, cervically stimulated (CS) females suppresses the nocturnal surge of prolactin. To determine if the inhibitory effects of the MPOA operate through the DMN-VMN, electrical stimulation was applied to the MPOA of conscious ovariectomized female rats bearing bilateral electrolytic lesions of the DMN-VMN. In the first experiment, control (sham-stimulated, sham-lesioned) CS females exhibited normal nocturnal surges which peaked at 03.00 h. MPOA stimulation (01.00–05.00 h) of both sham-lesioned and DMN-VMN lesioned CS females inhibited the release of their nocturnal surges. This suggests that the inhibitory function of the MPOA is independent of the DMN-VMN. MPOA stimulation can induce the release of a diurnal surge if the females are anesthetized with pentobarbital. In the second experiment, MPOA stimulation (15.00–19.00 h) of sham-lesioned anesthetized females produced elevated prolactin levels with significant peaks at 15.30 and 19.00 h. Anesthetized females with DMN-VMN lesions did not respond to MPOA stimulation with any change in prolactin secretion. Such data show that the stimulatory function of the MPOA requires an intact DMN-VMN. The data suggest that the MPOA does not operate through or affect the activity of the DMN-VMN for regulation of the nocturnal surge. The stimulatory role of the MPOA, however, does require interaction with an intact DMN-VMN for control of the diurnal su

ISSN:0028-3835    

DOI:10.1159/000124079

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

The hypothalamic action of progesterone on the regulation of LH secretion was investigated in a rat model ideally suited for the study of progesterone effects under conditions in which the animal is sensitive to progesterone but does not have an estrogen-induced gonadotropin surge. Immature female rats were ovariectomized at 26 days of age and treated for 4 days with a subphysiological dose of 0.1 µg/kg/day estradiol followed by the injection of either 0.8 or 3.2 mg/kg progesterone at 9.30 a.m. on day 5. Serum LH levels were significantly depressed below control and pretreatment values 30 min after either dose of progesterone. At this time, 0.8 mg/kg progesterone administration resulted in a significant increase in MBH-LHRH and plasma LHRH levels. In contrast, the administration of the 3.2 mg/kg dose of progesterone did not result in an increase in MBH-LHRH levels. By 2 p.m., rats receiving 0.8 mg/kg progesterone, but not those receiving 3.2 mg/kg progesterone, showed a significant increase in serum LH concentration and this elevation was maintained at 4 p.m. The increase in serum LH levels was preceded by a rise in MBH-LHRH levels by 1 p.m., followed by a fall at 2 p.m. The LH rise was maintained during the rise and replenishment of the MBH-LHRH by 3 p.m. Between 2 and 3 p.m. the replenishment of MBH-LHRH levels was accompanied by a fall in POA-LHRH levels. These results show that under the proper estrogen priming, and even in the absence of an estrogen-induced gonadotropin surge, a single injection of progesterone can induce changes in hypothalamic LHRH that are similar to those observed on proestrus in the cycling rat, leading to the gonadotropin surge

ISSN:0028-3835    

DOI:10.1159/000124080

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

Because of some indication that FSH secretion is less dependent than LH secretion on GnRH in vivo, we performed experiments to examine the effects of a GnRH antagonist (antag) on LH and FSH secretion. We first showed that pituitary cells superfused with GnRH showed a similar pattern of suppressed secretion of both LH and FSH in response to addition of antag. In contrast, antag administration to ovariectomized rats had differing effects on LH and FSH secretion. Serum LH was suppressed in a dose-dependent fashion by 2 h (20–50% of control values). Recovery from the lower doses of antag was seen by 12 h, but the two highest doses maintained serum LH levels at 10% of control values for 72 h. In contrast, the effect on serum FSH was not manifested until 12 h. FSH was maximally decreased only to 40–60% of control values. The two highest doses maintained this effect for 72 h. These results reinforce previous suggestions that FSH secretion in vivo may occur independently of acute changes in GnRH secretion, and may have an GnRH-independ-ent compon

ISSN:0028-3835    

DOI:10.1159/000124081

出版商:S. Karger AG    

年代:1985

数据来源: Karger