PubMed Health⌕ Search

Biomedical subjects

R F Weick

Publications and source records attributed to R F Weick.

At least 19 recordsLinked to original sources
PubMed1995

Role of VIP in the regulation of LH secretion in the female rat.

Vasoactive intestinal peptide (VIP) is found within neurons throughout the body. It influences the secretion of several hormones of the anterior pituitary by neural and pituitary actions. We review work from our laboratory that indicates that VIP inhibits the secretion of luteinizing hormone (LH) by a hypothalamic action. Experiments involving neural lesions indicate that VIP acts on the receptor field in the paraventricular nuclei of neurons whose cell bodies are located in the suprachiasmatic nuclei. The effect on LH secretion is subsequently mediated by a nonVIPergic pathway, which does not appear to involve either dopamine or endogenous opioids. Experiments with the specific VIP antagonist, [4Cl-D-Phe6,Leu17]VIP, indicate that the actions on LH secretion of VIP and of the related peptides, growth hormone-releasing hormone and secretin, are mediated by VIP-preferring receptors. VIP also blocks the steroid-induced LH surge in the ovariectomized rat. The VIP antagonist induces a significant, but small increase in LH secretion in the intact rat, indicating that VIP has a modulatory, rather than deterministic, role in the regulation of LH secretion.

Animals↗
PubMed1993

The effect of nalmefene on pulsatile secretion of luteinizing hormone and prolactin in men.

Luteinizing hormone (LH) and prolactin are released in pulses which are relatively synchronous in the luteal phase of the menstrual cycle in women. The concordance of LH and prolactin pulses in normal men has not been reported. The objectives of this study were firstly to determine whether LH and prolactin pulses are synchronous in men, and secondly to examine the effects of naloxone and a new orally active opiate antagonist, nalmefene, on LH and prolactin release in men. Three groups of normal male subjects received saline infusion (control n = 5), naloxone infusion (2 mg/h; n = 5) or nalmefene (10 mg p.o.; n = 6). Blood samples were collected every 15 min for 2 h before and 6 h after study medication for determination of LH, prolactin and testosterone by radioimmunoassay. Both naloxone and nalmefene resulted in a significant increase in LH pulse frequency and in mean serum LH and testosterone concentrations with no change in LH pulse amplitude, prolactin pulse frequency or amplitude. In controls, 61% of LH pulses were synchronous with prolactin pulses. There was a decrease in concomitance of LH and prolactin pulses with naloxone (48%) and nalmefene (24%; P < 0.025) administration. In contrast, 52% of prolactin pulses were concomitant with LH pulses in controls, while naloxone (100%) but not nalmefene (67%) resulted in a significant (P < 0.01) increase in pulse synchrony. The difference observed between naloxone and nalmefene on prolactin--LH pulse synchrony is probably due to differential opioid receptor activity at the pituitary and hypothalamic level.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Effect of [4Cl-D-Phe6,Leu17]VIP on the inhibition of pulsatile LH release by VIP and related peptides in the ovariectomized rat.

Pulsatile LH secretion in the ovariectomized (OVX) rat is inhibited by intracerebroventricular (icv) infusion of vasoactive intestinal peptide (VIP). VIP, rat growth hormone-releasing hormone (rGRH) and secretin with and without an antagonist to VIP, [4Cl-D-Phe6,Leu17]VIP (VIPA), were infused icv into OVX rats. Both VIP and rGRH at an infusion rate of 3.5 nmol/h lowered mean LH concentrations and pulse frequency without affecting pulse amplitude, and these effects were blocked by concurrent infusion of VIPA (10.5 nmol/h). Secretin also inhibited pulsatile LH secretion, but was only fully effective at the higher infusion rate of 7 nmol/h. This effect of secretin was also blocked by concurrent infusion of 10.5 nmol/h of VIPA. These results suggest that all three of these peptide hormones inhibit pulsatile LH secretion by an interaction with VIP receptors.

Animals↗
PubMed1992

Vasoactive intestinal peptide inhibits the steroid-induced LH surge in the ovariectomized rat.

The LH surge was induced in ovariectomized rats by sequential treatment with oestradiol benzoate and progesterone. Vasoactive intestinal peptide (VIP) or saline was infused into the third cerebral ventricle from 13.30 to 16.30 h on the afternoon of the anticipated LH surge. Two blood samples were taken by jugular puncture from each animal, one at 12.00 h as a control sample and the other at 16.00, 18.00, 20.00 or 22.00 h. Saline-infused animals showed a normal LH surge, with mean plasma LH concentrations reaching a peak at 18.00 h, declining by 20.00 h and reaching control (12.00 h) levels by 22.00 h. Plasma LH in animals infused with VIP was not significantly higher than control levels at 16.00 or 18.00 h. By 20.00 h, mean LH levels in VIP-infused rats had risen to the levels seen at that time in saline-infused rats, and by 22.00 h LH had returned to control levels in VIP-infused animals. We interpret these findings to mean that VIP inhibits LH secretion during the LH surge. It does not block the surge completely, as pentobarbital during the critical period would have done; nor does VIP appear to affect the timing of the LH surge. Rather, VIP inhibits the increased LH secretion rates of the LH surge only during the period of VIP treatment and for a short time afterward.

Animals↗
PubMed1990

Effects of lesions of the suprachiasmatic and paraventricular nuclei on the inhibition of pulsatile luteinizing hormone release by exogenous vasoactive intestinal peptide in the ovariectomized rat.

Vasoactive intestinal peptide (VIP) inhibits pulsatile luteinizing hormone (LH) secretion in the ovariectomized rat. Hypothalamic nuclei known to contain VIPergic neurons were destroyed electrolytically to determine whether either an increased response or a loss of response to exogenous VIP would result. Bilateral electrolytic lesions were made of either the suprachiasmatic (SCN) or paraventricular (PVN) nuclei in separate experiments; all animals received an intracerebroventricular cannula at the same time. Sham-lesioned animals were used as a control. One week later, a catheter was placed in the jugular vein of each rat and, after a recovery period of at least 2 h, blood samples were taken every 5 min for 3 h. After a control period of 1.5 h, either VIP or saline was infused into the third ventricle for an additional 1.5 h. Two doses of VIP were used: 3.5 nmol/h, previously shown to be inhibitory, and 0.4 nmol/h, which is ineffective in ovariectomized rats. LH was measured in the plasma by radioimmunoassay. The high dose of VIP lowered mean LH levels and pulse frequency but had no effect on pulse amplitude in both sham-lesioned and SCN-lesioned rats. The low dose of VIP did not affect pulsatile LH patterns in sham-lesioned rats, but did lower mean LH and pulse frequency in SCN-lesioned rats, indicating a denervation hypersensitivity subsequent to SCN lesions. Destruction of the PVN abolished the inhibitory effect of the high dose of VIP on pulsatile LH release. The low dose of VIP was ineffective in both PVN- and sham-lesioned animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Responses of luteinizing hormone (LH) and follicle-stimulating hormone levels to exogenous gonadotropin-releasing hormone during the estrogen-induced LH surge in the ovariectomized rhesus monkey.

Experiments were performed to study the responsiveness of the pituitary to gonadotropin-releasing hormone (GnRH) during the dynamic changes in gonadotropin secretion associated with the estrogen-induced luteinizing hormone (LH) surge in the ovariectomized (OVX) rhesus monkey. Silastic capsules filled with estradiol-17-beta were implanted subcutaneously in ovariectomized rhesus monkeys, resulting in an initial lowering of circulating LH and follicle-stimulating hormone (FSH) concentrations followed by an LH-FSH surge. GnRH was injected intravenously just before estrogen implantation, during the negative feedback response and during the rising, the peak, and the declining phases of the LH surge. The LH and FSH responses during the negative feedback phase were as large as those before estrogen treatment (control responses). During the rising phase of the LH surge, the acute response to GnRH injection did not differ significantly from the control response, but the responses 60 and 120 min after injection were somewhat increased. During the declining phase of the LH surge, the pituitary was not responsive to exogenous GnRH, although LH probably continued to be secreted at this time since the LH surge decreased more slowly than predicted by the normal rate of disappearance of LH in the monkey. We conclude that an increased duration of response to GnRH may be an important part of the mechanism by which estrogen induces the LH surge, but we do not see evidence of increased sensitivity of the pituitary to GnRH as an acute releasing factor at that time.

Animals↗
PubMed1989

Vasoactive intestinal peptide inhibits luteinizing hormone secretion: the inhibition is not mediated by dopamine.

Vasoactive intestinal peptide (VIP) is a neuropeptide that is present in the hypothalamus and is probably a neuroendocrine regulator. The effect of VIP on pulsatile LH secretion in the long-term ovariectomized rat was re-examined in the light of earlier conflicting reports. VIP or saline was infused into the third ventricle at the rat of 15 microliters/h and blood was sampled frequently before and during the infusion. VIP at 3.5 nmol/h significantly depressed mean LH levels (p less than 0.05) and lowered pulse frequency (p less than 0.05), but had no effect on LH pulse amplitude (p greater than 0.05). VIP at lower levels was not consistently effective, and intraventricular saline was without influence. We examined indirectly whether the site of action of VIP (3.5 nmol/h) was the brain or pituitary by injecting various doses of gonadotropin-releasing hormone (GnRH; 0.5-4.0 ng/100 g BW i.v.) during VIP-induced inhibition of LH secretion and in saline-infused controls. VIP did not alter the response of the pituitary to GnRH or the slope of the GnRH-LH dose-response curve (p greater than 0.05). We conclude that the inhibitory action of VIP on pulsatile LH secretion is probably exerted in the hypothalamus. To test the hypothesis that dopamine mediates the inhibitory effects of VIP (3.5 nmol/h), animals were pretreated with the dopamine receptor blocking agent pimozide (1.26 mg/kg) in an attempt to block the actions of VIP. Pimozide did not affect the response of LH to VIP infusion (p greater than 0.05). We conclude that dopamine is not a likely mediator of the action of VIP.

Animals↗
PubMed1987

Evidence for reorganization of the neuroendocrine centres regulating pulsatile LH secretion in rats receiving neonatal monosodium-L-glutamate treatment.

Previous research has shown that the combination of anterior hypothalamic deafferentation (AHD) and electrolytic lesions of the anterior part of the arcuate nuclei blocks pulsatile LH secretion in ovariectomized rats, but that neither lesion alone was effective. Furthermore, the combination of AHD with arcuate lesions produced by neonatal treatment with monosodium-L-glutamate (MSG) does not block pulsatile LH release. To distinguish between the various possible reasons for this result, AHD and electrolytic lesions of the arcuate nuclei were combined in rats which had been treated neonatally with MSG or saline of equal osmolarity. One week after brain surgery, venous catheters were installed and blood samples taken at 5-min intervals for up to 3 h for assay of plasma LH. Rats treated with MSG and bearing AHD and electrolytic lesions of the arcuate nuclei continued to show pulsatile secretion of LH. Where the electrolytic lesions were posterior and dorsal to the anterior arcuate nuclei, however, LH release was blocked whether AHD was performed or not, but only in rats treated with MSG. None of the lesion combinations blocked pulsatile LH secretion in rats treated with saline. These results suggest that neonatal MSG treatment leads to a reorganization of the hypothalamus such that the role normally played by the arcuate nuclei in the regulation of pulsatile LH secretion is taken over by other hypothalamic structures.

Animals↗
PubMed1986

Effects of anterior hypothalamic deafferentation and neonatal monosodium-L-glutamate treatment on pulsatile LH secretion in the castrated rat.

Previous research has shown that electrolytic lesions of the anterior arcuate nuclei combined with anterior hypothalamic deafferentation (AHD) blocked pulsatile luteinizing hormone (LH) release in the ovariectomized rat, but that neither lesion was sufficient by itself. This led to the hypothesis that two separate neural pathways were capable of effecting pulsatile LH secretion, which was tested in another way in the present study. Newborn rats were injected with monosodium glutamate (MSG), a treatment which damages the arcuate nuclei, or NaCl of the same osmolarity as a control. As adults, the rats were gonadectomized and 2 weeks later, AHD or sham AHD was performed. One week after that, the rats were catheterized, and small blood samples were taken every 5 min for 3 h. Plasma was assayed for LH by radioimmunoassay. Neither MSG alone, AHD alone, nor the combination affected the number of animals with pulsatile LH patterns. In female rats, MSG treatment slightly decreased pulse frequency, while AHD depressed mean LH levels in male rats. No differences were seen in LH pulse amplitude. These results suggest either that MSG spares those neurons of the arcuate nuclei which are important for LH secretion, that electrolytic lesions of the arcuate nuclei destroy fibres of passage which are important for LH release, or that functional reorganization of the systems controlling LH release occurs following neonatal MSG treatment.

Afferent Pathways↗
PubMed1986

Hyperresponsiveness to the inhibitory action of dopamine agonists on luteinizing hormone secretion in the monosodium-L-glutamate-treated, orchidectomized rat.

The tuberoinfundibular (A12) dopaminergic pathway, which originates in the arcuate and periventricular nuclei, is thought to play an inhibitory role in the regulation of episodic luteinizing hormone (LH) secretion. Neonatal treatment of rats with the neurotoxin monosodium-L-glutamate (MSG) causes extensive damage to the arcuate nuclei and up to 60% depletion of dopamine (DA) in the mediobasal hypothalamus. We hypothesized that such DA depletion should result in a hyperresponsiveness to subsequent administration of a DA agonist. To test this hypothesis, male rats were treated neonatally with MSG. Control rats received injections of equiosmotic saline. As adults the rats were orchidectomized and fitted with indwelling venous catheters. Blood samples were taken from these unanesthetized, unrestrained rats at 5-min intervals for a 1-hour period, at which time the animals received an intraperitoneal injection of one of the following drugs: apomorphine (0.8 mg/kg, a DA receptor agonist), bromocriptine (8.0 mg/kg, a DA receptor agonist), 0.9% saline (vehicle for apomorphine) or 95% ethanol (vehicle for bromocriptine). Blood sampling was continued for a further 2-2.5 h. Plasma LH was measured by RIA. Both apomorphine and bromocriptine produced striking inhibition of circulating LH levels in MSG-treated rats. Neither of the control treatments altered pulsatile LH secretion patterns. Administration of exogenous gonadotropin-releasing hormone produced LH peaks in all animals so treated, including those whose endogenous LH secretion had been inhibited by the DA agonists. These findings suggest that the depletion of DA induced by neonatal MSG treatment results in a supersensitivity to DA agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Characteristics of pulsatile luteinizing hormone secretion in middle-aged ovariectomized rats.

Experiments were performed to characterize the pulsatile patterns of circulating luteinizing hormone (LH) in the middle-aged ovariectomized (OVX) rat. Frequent blood samples were taken from OVX rats at 6, 7-8, and 9-10 mo of age, and LH was measured by radioimmunoassay. Rats had been OVX either 2 wk (STO) or 10-20 wk (LTO) previously. Mean LH levels were significantly lower with increasing age, reflecting effects on both pulse amplitude and pulse frequency. Mean LH levels were higher in LTO than STO groups, reflecting primarily an increase in pulse amplitude, but there was also a small, significant decrease in pulse frequency with increased time following OVX. In a second experiment, a random selection of the rats in the STO groups was tested again 10 wk after OVX. A significantly higher number of 9- to 10-mo-old rats had pulsatile patterns at 10 wk than at 2 wk following OVX. Furthermore, mean plasma LH concentrations were higher in all three groups. We conclude that decreases in several parameters of LH secretion are seen in middle-aged OVX rats, at the time when irregularities are first seen in the estrous cycle in the intact rat.

Aging↗
PubMed1984

Inhibitory effects of estrogen and progesterone on several parameters of pulsatile LH release in the ovariectomized rat.

Recent reports on the effects of progesterone on the frequency of pulsatile LH release in several species have compelled a reevaluation of the regulation of pulsatile LH secretion by gonadal steroids in the rat. Long-term ovariectomized (OVX) adult rats were given Silastic implants filled with estradiol-17 beta in oil, and blood samples were taken every 5 min for 3 h, either 1 or 2 days later. Compared with the control group (empty Silastic capsules), estrogen-treated animals had significantly lower mean plasma LH concentrations, because of a significant increase in the time between pulses, pulse amplitude not being significantly affected. In a second experiment, it was determined that progesterone alone had no significant effect on pulse amplitude, frequency or mean plasma LH concentrations. In a third experiment, OVX animals received estrogen-filled (or empty) capsules on 1 day followed by progesterone-filled (or empty) capsules on the next day, and frequent blood samples were taken on the following day. Two-way analysis of variance showed significant inhibitory effects of estrogen on mean LH levels, pulse amplitude and pulse frequency. Progesterone lowered the pulse amplitude significantly, but had no effect on pulse frequency, unlike its reported effects in other species. There were no significant interactions between estrogen and progesterone on any parameter tested, indicating that there is no synergism between the two steroids under these conditions. We conclude that estrogen is the principal ovarian hormone restraining LH secretion in the long-term OVX rat and that progesterone has only a modest effect, even in the presence of estrogen.

Animals↗
PubMed1983

Separate negative feedback effects of estrogen on the pituitary and the central nervous system in the ovariectomized rhesus monkey.

The site(s) of the negative feedback action of estrogen on gonadotropin secretion were studied in the ovariectomized rhesus monkey by observing the serum LH and FSH responses to intravenous GnRH injections at various times after implantation of Silastic capsules filled with estrogen. Circulating estrogen concentrations produced by the capsules were within the normal midcycle range for this species. Four h after estrogen implantation, no LH or FSH response was seen to the GnRH injection, indicating a suppressive effect of the steroid directly on the pituitary. Twelve and 22 h after estrogen implantation, however, the LH and FSH responses were equal to or larger than control responses. Since preinjection LH and FSH levels were below control values at these times and the pituitary responded to exogenous GnRH, it appears that endogenous GnRH secretion was affected, indicating an inhibitory action of estrogen on the central nervous system. Thus these experiments suggest 2 separate negative feedback actions of estrogen: a transient one directly on the pituitary and a longer lasting effect on the central nervous system.

Animals↗
PubMed1982

Stimulation of single unit activity in the preoptic area and anterior hypothalamus, and secretion of luteinizing hormone, by ovarian steroids in ovariectomized rats with diencephalic islands.

The spontaneous activity of 454 single hypothalamic neurons was recorded in 42 chronically ovariectomized rats after severance of all neural connections with the diencephalon. In 15 of these diencephalic island preparations progesterone was administered immediately before the recording session (and just after deafferentation of the diencephalon) and oestrogen 72 h beforehand. Thirteen rats were given two injections of oestrogen at these times and the remaining 14 rats were similarly treated with equal volumes of oil. Blood samples were obtained from all rats just before each hormone or oil injection, and 4, 5, 6 and 7 h after the second one, for subsequent measurement of plasma luteinizing hormone (LH) concentration. Only the group of rats given progesterone at the time of the second injection showed a significant increase in plasma LH concentration during the recording period. There was however some individual variation and the greatest LH surge was obtained from a rat given two injections of oestrogen. For steroid-treated rats the size of the LH surge was significantly correlated (P less than 0.01) with the mean firing rate of the neurons recorded in the preoptic and anterior hypothalamic areas (p.o.--a.h.). No similar correlation could be established for p.o.--a.h. cells recorded in oil-treated rats or for cells recorded in other parts of the hypothalamus in steroid-treated rats. The mean firing rate of all p.o.--a.h. cells recorded from rats treated with oestrogen followed by progesterone was significantly higher (P less than 0.05) than in either of the other two groups of animals. The oestrogen--progesterone treatment also significantly changed the regularity of discharge of the slow firing (less than 2 Hz) p.o.--a.h. cells, but this phenomenon could not be related to any alteration in plasma LH concentration. The experiments have demonstrated for the first time that the magnitude of the steroid-stimulated LH surge in ovariectomized rats is significantly correlated with the increase in the electrical activity of p.o.--a.h. neurons.

Action Potentials↗
PubMed1981

Development of pulsatile LH release as a function of time following ovariectomy in the rat.

Since pulsatile patterns of luteinizing hormone (LH) secretion have been reported in long-term ovariectomized (OVX) rats, but not intact rats, the patterns of tonic LH secretion were studied in intact female rats and 2, 4 and 8 days after OVX. Blood samples were taken every 10 min for 2 h from intact rats, catheterized the previous day, during the late morning of diestrus-1, proestrus and estrus. Mean LH concentrations were 55 +/- 7 ng/ml and did not differ among days. A single increase of circulating LH suggestive of one pulsatile release was seen in 4 of the 14 rats, but no animal showed the regular, repeated increases characteristic of long-term OVX animals. 2 days after OVX, mean LH concentrations were 156 +/- 10 ng/ml and patterns characteristic of regular pulsatile releases of LH were seen in 2/6 animals, with occasional pulsatile discharges in another 3. By 4 days after OVX, all 6 animals showed pulsatile patterns of LH, and mean LH concentrations were 190 +/- 32 ng/ml. By day 8, mean LH levels had increased significantly, to 357 +/- 44 ng/ml, and peak and nadir levels, as well as LH pulse amplitude, had all risen significantly. No significant difference in frequency of LH pulses was noted after OVX, although they seemed to occur more frequently at 8 days. These results suggest that pulsatile discharges of LH in the intact rat are either heavily suppressed or infrequent but that they become a prominent feature of LH secretion soon after OVX.

Animals↗
PubMed1981

Secretion of luteinizing hormone in ovariectomized adult rats treated neonatally with monosodium glutamate.

We have studied the possible effects of monosodium glutamate (MSG) on LH secretion in ovariectomized rats. In experiment 1 MSG-treated and control rats were given oestradiol benzoate at noon and 72 h later half the rats in each group were given a second injection of oestradiol benzoate or progesterone. Blood samples were taken immediately before and 6 h after these i.m. injections. At 78 h there were no significant differences in plasma LH concentration measured in the two groups of rats given progesterone or in the two groups given a second injection of oestradiol benzoate although for both MSG-treated and control rats progesterone produced a significantly (P less than 0.01) greater LH surge than did oestradiol benzoate. In experiment 2 100 ul blood samples were collected at 5-min intervals for up to 3 h from MSG-treated and control rats. For rats showing more than one pulsatile discharge of LH, peak and trough values for plasma LH concentrations were no significantly influenced by MSG treatment. However the mean pulse height was significantly (P less than 0.001) greater in the MSG-treated group than in control rats. Pulsatile release stopped more quickly in the MSG-treated rats and their mean plasma LH concentration after 120 min of blood sampling was significantly (P less than 0.05) lower than that obtained in the control animals. Thus, although some aspects of LH secretion seem to be significantly different in MSG-treated rats, these effects may result from the greater sensitivity of the MSG-treated animals to experimental manipulation.

Animals↗