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1.
E Ortega  J Frias  E Rodriguez  E Ruiz 《Life sciences》1988,43(17):1349-1354
The intracerebroventricular (ICV) injection of ACTH (1-24) (0.1, 1.0 and 2.5 micrograms) to adult conscious ovariectomized (OVX) rats caused a dose-related inhibition of plasma LH at 10 min postinjection. The ICV injection of ACTH (1-24) (2.5 micrograms) to OVX rats in the absence or presence of a single dose of estradiol benzoate (OVX + EB): a) Decreased significantly plasma LH levels in OVX rats at 10 and 30 min postinjection. b) Decreased significantly plasma LH levels in (OVX + EB) rats at 10 min but not at 30 min postinjection. c) Did not change plasma FSH levels at 10 or 30 min postinjection in both (OVX) or (OVX + EB) rats. d) Did not change plasma ACTH levels at 10 or 30 min postinjection in (OVX) rats. Our observation suggest that ACTH (1-24) inhibited plasma LH, possibly through brain sites of action.  相似文献   

2.
We determined the dose-response relationship and examined the time related effect of CRF (corticotropin releasing factor) injected directly into the median eminence (ME) on LH and FSH secretion in conscious female rats of different steroid status. Doses of 0.25, 0.75, 1, and 1.5 nM CRF dissolved in 1l of water were injected into the ME in 5 experimental groups of rats: Short-term (2 days) ovariectomized (sOVX); long-term (3–4 weeks) ovariectomized (lOVX); lOVX primed by estradiol benzoate (EB) 4 h before the experiment (lOVX+E); lOVX primed by EB 36 h before the experiment (lOVXE) and lOVX primed by EB 72 h and progesterone 6 h before experiment (lOVXP). Blood was collected at 30, 60, 90, and 120 min postinjection to determine LH and FSH by RIA. CRF at the doses of 0.75, 1, and 1.5 nM significantly decreased serum LH levels in all groups. The dose of 0.25 nM CRF was ineffective. The highest dose (1.5 nM) of CRF had no effect on serum FSH levels. The results suggest that CRF inhibits LH secretion, at least in part, by a central action on GnRH release in the ME, and that this effect is independent of the estrogen/progesterone status of the animal.  相似文献   

3.
To evaluate whether the median eminence (ME) is a site of action of CRF (corticotropin releasing factor) on GH secretion and to determine the possible role of estradiol and progesterone in modifying theses secretion, we injected CRF (0.25, 0.75, 1, and 1.5 nmol of peptide dissolved in 1 μl of water) directly into the ME in three experimental groups of rats: Long-term ovariectomized (OVX); OVX primed by estradiol (OVX±E) and OVX primed by estradiol plus progesterone (OVX±EP). Blood was collected to determine GH (30, 60, 90, and 120 min postinjection) Serum T3, T4, and glucose levels were measured in OVX±E rats 30 min postinjection. CRF at all doses studied significantly decreased serum GH levels in the three experimental groups. Serum T3, T4, and glucose levels were unchanged after CRF administration. The results suggest that: CRF inhibits “per se” GH secretion, at least in part, by a central action in the ME. The inhibitory effect of CRF on GH is independent of the estrogen/progesterone status of the animal. CRF at ME levels may participate in a variety of stress-related responses, including growth inhibition, through GH suppression.  相似文献   

4.
Frias  J.  Puertas  A.  Ruiz  E.  Ortega  E. 《Neurochemical research》1997,22(2):171-174
We determined the dose-response relationship and examined the time-related effect of CRF (corticotropin releasing factor) injected directly into the Median Eminence (ME) on LH secretion in conscious intact and castrated male rats. Doses of 0.25, 0.75, 1, and 1.5 nmol CRF dissolved in 1 l of saline (or saline only in the controls) were injected into the ME and blood samples collected 30, 60, 90, and 120 min postinjection to determine by RIA serum LH. CRF at doses of 0.75, 1 and 1.5 nmol significantly decreased serum LH in castrated and intact animals. The lower dose of CRF did not decrease LH in the two groups studied. The results suggest that in males as in females, CRF inhibits by itself LH secretion, at least in part, by a central action in the ME; the inhibitory effect of CRF on LH is similar in castrated and intact males; the dose of 0.25 nmoles of CRF was ineffective in decreasing LH and finally that CRF at ME levels may participate in a variety of stress-related responses, including reproduction inhibition, through LH suppression.  相似文献   

5.
Estradiol-benzoate (EB) injected into previously ovariectomized (OVX) rats, increased pituitary ATPase activity 69% over controls, within one hour of treatment. Twelve hours after injection, ATPase activity was not significantly different from controls. Progesterone [(P): 5mg/100gBW] administered in conjunction with EB elicited an analogous response. AT at time of EB and EB+P induced increments in pituitary ATPase activity, plasma LH levels were dramatically reduced to normal, intact diestrous control levels. Post-castrational elevations in FSH were also suppressed after one hour of treatment with EB, but not following EB+P administration. The results suggest that the inhibitory actions of EB and EB+P on post-castrational LH levels may be related to modulation by these steroids of pituitary membrane ATPase activity.  相似文献   

6.
We determined the dose-response relationship and examined the time-related effect of CRF (corticotropin releasing factor) injected directly into the Median Eminence (ME) on GH (growth hormone) secretion in conscious intact and castrated male rats. Doses of 0.25, 0.75, 1, and 1.5 nmol CRF dissolved in 1 l of saline, or saline alone in the controls, were injected into the ME, and blood samples collected through indweling catheters implanted in the jugular vein, 30, 60, 90, and 120 min post-injection to determine plasma GH levels by RIA. After 120 min the animals were decapitated. Trunk blood of decapitated animals was used to determine plasma testosterone and glucose levels. CRF at all the doses studied significantly decreased plasma GH in castrated and intact animals. The results suggest that in male as in female rats, CRF inhibits by itself GH secretion, at least in part, by a central action in the ME; all the doses of CRF studied suppressed GH secretion in castrated and intact males; finally, CRF at ME levels may participate in a variety of stress-related responses, including growth inhibition, through GH suppression.  相似文献   

7.
Summary 1. Intact or ovariectomized (OVX) cyclic rats injected or not with RU486 (4 mg/0.2 ml oil) from proestrus onwards were bled at 0800 and 1800h on proestrus, estrus and metestrus. Additional RU486-treated rats were injected with: LHRH antagonist (LHRHa), estradiol benzoate (EB) or bovine follicular fluid (bFF) and sacrified at 1800 h in estrous afternoon. LH and FSH serum levels were determined by RIA.2. RU486-treated intact or OVX rats had decreased preovulatory surges of LH and FSH, abolished secondary secretion of FSH and hypersecretion of FSH in estrous afternoon. The latter was decreased by LHRHa and abolished by EB or bFF. In contrast, EB induced an hypersecretion of LH in RU486-treated rats at 1800h in estrus.3. It can be concluded that in the absence of the proestrous progesterone actions, the absence of the inhibitory effect of the ovary in estrus evoked a LHRH independent secretion of FSH.  相似文献   

8.
We have reported earlier that administration of lithium, the widely-used drug for the treatment of acute mania and prophylaxis of recurrent manic-depressive bipolar disorders, leads to a disruption of estrous cycle and a significant suppression of the proestrous surge of luteinizing hormone (LH) in a number of laboratory rodents. In this report we have examined the effects of this antimanic drug on plasma and pituitary levels of LH and follicle stimulating hormone (FSH) in rats following ovariectomy (OVX), an altered endocrine state in which the levels of serum LH and FSH are highly and chronically elevated. Adult OVX rats, maintained under standardized laboratory conditions (LD 12: 12; white lights on at 06.00 h, CST) were injected (ip) with lithium, 40 days post-operation, at a dosage of 3.0 and 2.0 mEq/Kg b. wt. for 3 and 7 days respectively (twice daily at 08.00 and 16.00 h). Control OVX rats received nothing or saline injections, whereas an intact control (C) received no surgical manipulation or drug injections of any kind. As expected, the levels of plasma LH and FSH in OVX (only) group showed nearly 6-fold and 75-fold increase respectively compared to those in C. Lithium injections in OVX rats for 3 and 7 days resulted in a significant reduction in plasma LH (P less than .005 and P less than .02 respectively) and FSH (P less than .001) levels when compared with those in the OVX control groups. Lithium also led to a significant reduction in the levels of pituitary LH after both 3 (P less than .02) and 7 days (P less than .02), but the levels of pituitary FSH remained unchanged. These results suggest that the pituitary gonadotropes constitute a definitive target for lithium's action, either directly or via the hypothalamus.  相似文献   

9.
10.
The effects of intravenous or intraventricular injection of synthetic ovine corticotrophin-releasing factor (oCRF) on plasma levels of anterior pituitary hormones were studied in conscious, ovariectomized (OVX) female rats and compared with the actions of the peptide on dispersed anterior pituitary cells from OVX female rats incubated in the presence of CRF. Third ventricular injection of oCRF in freely moving rats caused a significant increase in plasma levels of ACTH in a dose-related manner with a minimal effective dose of less than 0.5 micrograms (0.1 nmol). The effect was observable at 5 min after injection and persisted for the 60 min duration of the experiment. In contrast, growth hormone levels were significantly depressed within 15 min with a minimal effective intraventricular dose of 0.5 micrograms. The suppression persisted for the duration of the experiment but there was no additional effect of the higher dose of 5 micrograms. Plasma LH levels were also lowered by the highest dose of 5 micrograms (1.0 nmol) of oCRF, with the first significant lowering at 30 min. Lower doses had no effect on plasma LH. Plasma TSH levels were not significantly altered. Control injections of the 0.9% NaCl diluent were without effect on the levels of any of the hormones. Intravenous injection of similar doses of oCRF had no effect on plasma levels of GH or LH. The ACTH-releasing action of the oCRF preparation was confirmed by in vitro incubation of the peptide with dispersed anterior pituitary cells for 2 h. A dose-related release of ACTH occurred in doses ranging from 0.1-10 nM, but there were no effects on the release of the other anterior pituitary hormones. The results suggest that oCRF may act within the hypothalamus to suppress the release of GH and to a lesser extent LH. The stimulation of ACTH release following intraventricular CRF is presumably related to its uptake by portal blood vessels with delivery to the pituitary and stimulation of the corticotrophs.  相似文献   

11.
M Arisawa  G D Snyder  S M McCann 《Peptides》1989,10(4):763-766
The role of substance P (SP) on thyrotropin (TSH) secretion was investigated in ovariectomized (OVX) female, estrogen-primed OVX, and normal male rats. Third ventricular administration of SP induced a significant increase in plasma TSH levels when compared to control animals in E-primed OVX rats (p less than 0.001). The plasma TSH levels increased in a dose-related manner and reached maximum levels at 10 min after injection. In contrast, intraventricularly injected SP failed to alter plasma TSH levels in both OVX rats and normal male rats. Intravenous administration of SP dramatically stimulated TSH release in E-primed OVX rats (p less than 0.001), whereas SP had no effect on the release of TSH when injected in OVX rats and normal male rats. To investigate any direct action of SP on TSH release from the anterior pituitary gland, synthetic SP was incubated with dispersed anterior pituitary cells harvested from E-primed OVX rats and normal male rats. SP, in the dose range between 10(-8) M and 10(-6) M, failed to alter the release of TSH into the culture medium in vitro. These findings indicate that SP has a stimulatory role in the control of TSH release by an action on the hypothalamus but only in estrogen-primed rats.  相似文献   

12.
The direct effects of alpha- and beta-adrenergic agents on luteinizing hormone (LH) secretion in vitro by porcine pituitary cells and the participation of secondary messengers, adenosine 3'5'-monophosphate (cAMP) and guanosine 3'5'-monophospate (cGMP), in transduction of signals induced by adrenergic agents and gonadotropin-releasing hormone (GnRH) in these cells have been investigated. Pituitary glands were obtained from mature gilts, which were ovariectomized (OVX) 1 month before slaughter. OVX gilts, assigned to four groups, were primed with: (1) vehicle (OVX); (2 and 3) estradiol benzoate (EB; 2.5mg/100kg b.w.) at 30-36h (OVX+EB I) or 60-66h (OVX+EB II) before slaughter, respectively; (4) progesterone (P(4); 120mg/100kg b.w.) for 5 consecutive days before slaughter (OVX+P(4)). Anterior pituitaries were dispersed with trypsin and then pituitary cells were cultured (10(6) per well) in McCoy's 5a medium containing horse serum (10%) and fetal calf serum (2.5%) for 3 days, at 37 degrees C and under the atmosphere of 95% air and 5% CO(2). On day 4 of the culture, the cells were submitted to 3.5h incubation in the presence of GnRH (a positive control), alpha- and beta-adrenergic agonists (phenylephrine (PHEN) and isoproterenol (ISOP), respectively), and alpha- and beta-adrenergic blockers (phentolamine (PHENT) and propranolol (PROP), respectively). The culture media were assayed for LH (experiment I) and cyclic nucleotides (experiment II).In experiment I, addition of GnRH (100ng/ml) increased LH secretion by pituitary cells taken from gilts of all experimental groups. The effects of alpha- and beta-adrenergic agents on LH secretion by the cells depended on hormonal status of gilts. The LH secretion by pituitary cells of OVX gilts was potentiated in the presence of PHEN (10, 100nM, and 1microM) and PHENT (1microM), alone or in combination with PHEN (100nM) and by the cells derived from OVX+EB I and OVX+P(4) animals in response to PHEN (100nM) and ISOP (1microM). ISOP (1microM) also stimulated LH secretion by the cells taken from OVX+EB II gilts. In experiment II, GnRH (100ng/ml) increased cGMP production by pituitary cells obtained from all groups of gilts and cAMP secretion by the cells taken from OVX and OVX+P(4) animals. PHEN (100nM) decreased and PROP (1microM) enhanced cAMP production by pituitary cells derived from OVX+EB I and OVX gilts, respectively. Moreover, PHEN (100nM) reduced, while PHENT (1microM) stimulated the release of cGMP by pituitary cells taken from OVX+EB II animals. In turn, ISOP (100nM) decreased and increased cGMP production by the cells derived from OVX+EB II and OVX+P(4) gilts, respectively. PROP (1microM) potentiated cGMP accumulation by pituitary cells taken from OVX+EB I and OVX+P(4) animals.In conclusion, our results suggest that adrenergic agents can modulate LH release by porcine pituitary cells acting through guanyl and adenylyl cyclase and in a manner dependent on hormonal status of gilts.  相似文献   

13.
The development of estrogen feedback system on gonadotropin release during sexual maturation in female rats was studied. Animals (Wistar strain rats) were divided into 6 groups according to their ages; 10, 15, 20, 25, 30, and 35 days. Both LH and FSH levels in serum increased significantly in response to ovariectomy in all age-groups studied when measured one week postoperatively, though in the rats aged 10-15 days the increase in FSH following castration was only slight. In rats older than 25 days, the postcastration gonadotropin rise, calculated as a percent increase from the basal figure, decreased gradually with increasing age. Ovariectomized rats injected with estradiol benzoate (EB, 5 micrograms/100 g BW) showed significantly lower levels of both LH and FSH than those in castrated controls. However, the inhibitory action of EB on postcastration gonadotropin output was found to be relatively less effective in rats older than 25 days. Ovariectomized rats primed with EB were again injected with a 2nd dose of EB (5 micrograms/100 g BW) at noon 3 days after priming. The 2nd EB injection induced a significant rise in LH 6 h later in 30- and 35-day-old, though not in younger, animals. On the other hand, the FSH response to EB was markedly enhanced during days 15-25 of age. These results indicate that the estrogen negative feedback action on gonadotropin release is already operating in female rats at a very early age, and that the brain sensitivity to estrogen decreases slightly during the late prepubertal phase.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

14.
Studies were conducted to explore the hypothesis that the delayed sexual maturation of female rats induced by reduced food intake (R) may result partially from an altered negative feedback response to estrogen. Animals were placed on 60% of normal food intake at 20 days of age. Controls (C) were fed ad libitum. Rats were used for three different experiments at 31-32 days of age. In Experiment I, rats were ovariectomized (OVX) and injected subcutaneously for 4 days with varying doses of estradiol benzoate (EB). They were killed the day after the last injection. In Experiment II, rats were ovariectomized and killed in groups at 4, 12, 24, 48, 72, and 120 h after OVX. In Experiment III, they were castrated and 1 wk later received a single injection of 0.5 microgram EB. Groups were killed at 1, 2, 4, 8, and 24 h after injection. Sera from all experiments were assayed for follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin. Results of Experiment I indicate that the efficacy of EB for suppressing LH, but not FSH, secretion is increased significantly in R rats. In Experiment II, OVX resulted in a delayed increase in serum LH, but not FSH, concentrations of R rats when compared to C animals. Results of Experiment III indicate a delayed, but more prolonged, suppression of LH secretion by EB in R rats when compared to C rats. Prolactin secretion, on the other hand, increased earlier in R rats.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

15.
Third ventricular injections of vasoactive intestinal polypeptide (VIP) result in increased circulating levels of luteinizing hormone (LH) in conscious, freely moving, ovariectomized (OVX) rats. This effect of VIP has been hypothesized to be mediated via stimulation of luteinizing hormone-releasing hormone (LH-RH) secretion from hypothalamic neurons since VIP is incapable of stimulating LH release from rat pituitaries in vitro. To test this hypothesis, crude synaptosomes were prepared from OVX rat median eminence (ME) tissue. Release of LH-RH from these preparations displayed time and temperature dependencies. Additionally, depolarization-induced (elevated K+) LH-RH release was demonstrated to be Ca2+-dependent. VIP, in doses ranging from 1.5 · 10?9 M, was capable of stimulating significantly greater LH-RH release from ME synaptosomes than that from control preparations. VIP's close structural homolog, glucagon, was incapable at the same doses of stimulating increased LH-RH release. These findings offer an explanation for the effect of third ventricularly injected VIP on LH release and suggest a modulatory role for VIP in the hypothalamic control of LH secretion.  相似文献   

16.
The effect of the new opioid antagonist naltrexone-estrone azine (EH-NX) on pituitary luteinizing hormone (LH) secretion in the ovariectomized rat was studied. EH-NX is a hybrid between the steroid component estrone and the opioid antagonist naltrexone (NX). It is a potent and long-acting opioid antagonist in vitro and in vivo, but its effect upon in vivo LH secretion has not been tested before. The aims of the study were to investigate whether, unlike naltrexone, EH-NX can stimulate LH secretion without the need of additional estrogen pretreatment and whether EH-NX has peripheral estrogenic effects upon the uterine weight, when administered chronically to long-term ovariectomized rats. Female rats were injected subcutaneously with EH-NX 21 days after ovariectomy. The effects of EH-NX injections on LH secretion were compared to the effects of NX and estrone hydrazone (EH) alone, or in combination, with or without estradiol-benzoate (EB) pretreatment. Inhibition of LH secretion and uterine proliferation were observed in rats treated chronically with EH-NX in dosages of 0.250 mg/kg bw and higher. These effects were similar to those caused by EH and EB. In short-term OVX rats EH-NX appeared to act faster than EH. In contrast to NX, no stimulatory effect on LH secretion was seen with EH-NX in EB primed OVX rats. These results surprisingly demonstrate that EH-NX behaves like an estrogen and not like an opioid antagonist. The unexpected pharmacological profile of this new drug may open up doors for several medical applications.  相似文献   

17.
The effect of a transitory increase in plasma FSH and LH levels on puberty has been investigated. Hormonal changes were induced by bilateral ovariectomy (OVX) at 20 days of age followed by implantation of two ovaries (donor animals 20-day-old) beneath the kidney capsule 1, 2 or 3 days later. In an other group of animals the two interventions were made in reversed order. Rats in which OVX was made first showed early vaginal opening. If ovarian implantation preceded OVX, these two interventions did not affect the time of vaginal opening. More than 1/3 of the ovarian implanted animals exhibiting early opening of the vagina contained corpora lutea three days after vaginal opening. FSH and LH levels of OVX + ovary implanted rats were from the third day on following implantations markedly different from the OVX controls and were in the range of intact or sham-operated rats. The present findings indicate that a transitory increase in plasma gonadotropin levels around twenty days of age may lead to precocious puberty.  相似文献   

18.
To investigate the role played by the different rat gonadotroph oestrogen receptor (ER) pools in the effects of oestradiol-17beta (E2) on gonadectomy cells, two-week ovariectomised (OVX) rats were used. The basic experimental group of rats was injected with 3 mg of the selective ER modulator tamoxifen (TX) on days 15-20 after OVX. Groups of TX-treated OVX rats were additionally injected on days 18-20 after OVX with 10 microg oestradiol benzoate (EB), 1 mg of the selective ERalpha agonist propylpyrazole triol (PPT), or 1 mg of the selective ERbeta diarylpropionitrile (DPN). Negative and positive control groups were OVX rats injected over six days after OVX with 0.2 ml oil and EB, respectively. On day 21 after OVX, anterior pituitary glands were dissected out and divided into halves. One hemipituitary was processed for light microscopy and immunocytochemistry for betaLH subunit and progesterone receptor (PR), and the other hemipituitary for ultrastructural evaluation. Results showed that: gonadotrophs were the only pituitary cell type expressing PR; treatment with TX alone shrunk gonadectomy cells and induced both reorganization of membrane-enclosed intracellular organelles and PR expression, and treatment with DPN or EB, but not PPT, reduced the agonistic morphological effects of TX. Considering that TX activates nuclear ERalpha, the results indicate that activation of nuclear ERalpha is determinant for the reversal effects of E2 on gonadotrope morphology and PR expression, and the simultaneous activation of ERbeta modulates the action of ERalpha in an inhibitory fashion.  相似文献   

19.
To determine the role of arginine vasopressin (AVP) in stress-induced release of anterior pituitary hormones, AVP antiserum or normal rabbit serum (NRS) was micro-injected into the 3rd ventricle of freely-moving, ovariectomized (OVX) female rats. A single 3 microliter injection was given, and 24 hours later, the injection was repeated 30 min prior to application of ether stress for 1 min. Although AVP antiserum had no effect on basal plasma ACTH concentrations, the elevation of plasma ACTH induced by ether stress was lowered significantly. Plasma LH tended to increase following ether stress but not significantly so; however, plasma LH following stress was significantly lower in the AVP antiserum-treated group than in the group pre-treated with NRS. Ether stress lowered plasma growth hormone (GH) levels and this lowering was slightly but significantly antagonized by AVP antiserum. Ether stress also elevated plasma prolactin (Prl) levels but these changes were not significantly modified by the antiserum. To evaluate any direct action of AVP on pituitary hormone secretion, the peptide was incubated with dispersed anterior pituitary cells for 2 hours. A dose-related release of ACTH occurred in doses ranging from 10 ng (10 p mole)-10 micrograms/tube, but there was no effect of AVP on release of LH. The release of other anterior pituitary hormones was also not affected except for a significant stimulation of TSH release at a high dose of AVP. The results indicate that AVP is involved in induction of ACTH and LH release during stress. The inhibitory action of the AVP antiserum on ACTH release may be mediated intrahypothalamically by blocking the stimulatory action of AVP on corticotropin-releasing factor (CRF) neurons and/or also in part by direct blockade of the stimulatory action of vasopressin on the pituitary. The effects of vasopressin on LH release are presumably brought about by blockade of a stimulatory action of AVP on the LHRH neuronal terminals.  相似文献   

20.
Female rats in constant illumination (LL) fail to show the facilitation of LH release following steroid administration that is characteristic of animals in normal lighting. To determine whether this effect is mediated through changes in ovarian function, rats were spayed either at the time of placement into different lighting schedules (LL or a 14:10 light-dark (LD) schedule) or 10 weeks later, and their plasma LH responses to steroids were compared after an additional 3-week exposure to the experimental lighting conditions. To test the LH response, estradiol benzoate (EB) was injected at 12.00 h and followed 72 h later by injection of progesterone (P) or a second injection of EB. Neither steroid regime revealed differences in LH release between animals ovariectomized at the time of placement into LL and those spayed 10 weeks later. The duration of castration in animals in LD affected the LH response to a priming dose of EB, but not to a second dose of EB or to P. It is concluded that altered ovarian activity is not the factor which mediates the loss of a facilitatory response of LH release following administration of gonadal steroids to rats under constant illumination.  相似文献   

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