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At least 19 recordsLinked to original sources
PubMed1997

LHRH receptors and LHRH receptor-bearing cells in pituitaries of streptozocin diabetic male rats.

Streptozocin (STZ)-diabetic rats have low hypothalamic luteotropic hormone-releasing hormone (LHRH) secretion and various alterations of gonadotrope cells, among which low luteotropic hormone (LH) secretion. Possible causes for the gonadotrope disorders may be low hypothalamic LHRH secretion alone or combined with reduced (a) number of LHRH receptor sites, or (b) receptor to ligand affinity, or (c) of LHRH receptor-bearing cells. To clarify this question we determined by saturation and competition binding Bmax, KD and KA of the LHRH receptor sites and counted the receptor-bearing cells in pituitary glands of control and STZ-diabetic adult male rats. We found a single receptor class, the Bmax was strongly reduced in diabetic animals whereas both KD and KA were similar in the two groups. The number of LHRH receptor-bearing cells in diabetic animals was increased. Therefore a reduced number of receptor sites per gonadotrope cell occurs in our model. Since in the STZ-diabetic male rats the number of gonadotropes is increased, a higher number of receptor-bearing cells was observed. We conclude that the reduced LH secretion from the diabetic pituitary gland might be due to a reduced number of LHRH receptor sites in the pituitary gland. The increased number of receptor-bearing cells might partially compensate for this change.

Animals↗
PubMed1988

Opposite changes of pituitary and ovarian receptors for LHRH in ageing rats: further evidence for a direct neural control of ovarian LHRH receptor activity.

Hypophyseal and ovarian receptors for the neurohormone LHRH (LHRH-R) have been measured in young (3-4 months), middle-aged (8-11 months), constant estrous (CE, 10-14 months) and pseudopregnant (PR, 16-18 months) rats in order to study whether changes in hypothalamic and/or peripheral LHRH-like peptide production might precede and/or accompany the onset of reproductive failure observed in aging rats. Furthermore, we have investigated whether the neural efferent system from the brain to the ovary is affected with aging. The pattern of pituitary LHRH-R modifications during the estrous cycle of middle-aged rats shows lower LHRH-R levels on the second day of diestrus, resulting in a shift of the maximal LHRH binding capacity in the morning of proestrus. On the other hand, when comparing pituitary LHRH-R of animals exhibiting constant vaginal cornification (CVC) or repetitive PP with young estrus rats, no significant difference could be observed. Young rats responded to electrical stimulation (ES) of the medial preoptic area with an acute elevation of LHRH-R while ES performed in CVC, or PP animals resulted in a significant increase of hypophyseal LHRH binding capacity similar to the one observed in young estrous controls, indicating an impairment in the neural signals impinging in the pulse generating system, in old rats, and not an intrinsic defect of the LHRH-R per se. Ovarian LHRH-R concentration is higher in middle-aged cycling animals on the day of vaginal proestrus, compared to levels measured in young animals at any phase of the estrous cycle. Similarly, CE rats displaying CVC as well as PP animals show significantly higher numbers of LHRH-R with no change in affinity, than young estrus rats. CVC and PP rats receiving unilaterally an intraovarian injection of the potent LHRH antagonist, Ac-D-Cl-Phe1,2, D-Trp3, D-Phe6, D-Ala10, LHRH, showed an acute drop of LHRH-R measured within the treated ovary with no significant changes taking place in the vehicle-treated contralateral gland, suggesting that changes of endogenous ovarian LHRH-like peptide might participate in the mechanism(s) responsible for LHRH receptor increase observed in aging rats. In order to investigate the participation of a direct neural efferent pathway in ovarian LHRH-R regulation, young and old rats were subjected to spinal cord transection (above T10-T11). Bilateral transection of the spinal cord in young animals in the morning of proestrous markedly increased ovarian LHRH-R concentration in the afternoon (17.00 h) of the same day.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed1984

Maternal modulation of infantile ovarian development and available ovarian luteinizing hormone-releasing hormone (LHRH) receptors via milk LHRH.

In the rat, ovarian LHRH receptor content, measured by the binding of [125I]D-Ala6-Pro9-LHRH ([125I]A-LHRH) to ovarian membranes, declines during the days preceding the first preovulatory LH surge. The present results show that LHRH receptor content is low during neonatal-infantile days (days 5-15) and increases markedly thereafter to a maximum by day 25. When ovarian membranes from 10-day-old rats were pretreated with MgCl2 to dissociate endogenously bound hormone, LHRH-binding capacity increased to levels similar to those in untreated ovaries from 25-day-old rats. No significant increase was observed in ovaries from the latter group after MgCl2 exposure. Equilibrium association constants were similar (6-8 X 10(9) M-1) in MgCl2-treated and control ovaries, indicating that the increase in binding was not due to a change in receptor affinity. Pups prevented from suckling for various time intervals (1-24 h) exhibited an increase in available ovarian LHRH-binding sites which was maximal by 4 h. When pups were allowed to suckle subsequent to a 6-h fast, available ovarian LHRH receptors decreased rapidly (1 h). This decline was not due to a local increase in LHRH triggered by a neural reflex in response to suckling and/or stomach distension. Intragastric administration of milk reproduced the decline in available receptors induced by suckling, whereas stomach distension produced by saline was ineffective. Concomitant with the decline in receptors, suckling produced a significant increase in both stomach content and plasma levels of an LHRH-like material. Fractionation of acid milk extracts in Sephadex G-25 yielded two peaks, one in a position similar to that of synthetic LHRH. Milk LHRH purified in a C-18 Sep-Pak column displaced binding of [125I]A-LHRH to ovarian membranes and yielded a parallel binding curve in the LHRH RIA. This milk LHRH also released LH and FSH from pituitaries in vitro and inhibited FSH-induced estradiol and progesterone secretion from granulosa cells in culture in a dose-related manner, comparable to A-LHRH. The suckling-induced decrease in available LHRH receptors was prevented by iv administration of a specific LHRH antiserum directed against all 10 amino acids of native LHRH, suggesting that milk LHRH reaches the ovary via the bloodstream. The results indicate that an LHRH-like substance of milk origin binds to LHRH receptors in the pup ovary, thereby controlling receptor availability.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed1987

Solubilization of a large molecular weight form of the rat LHRH receptor.

The LHRH receptor has been solubilized from male rat anterior pituitary glands, using the zwitterionic detergent 3-((3-cholamidopropyl)-dimethylammonio)-1-propanesulphonate in the presence of a high concentration of sodium chloride. This method gave high yields (up to greater than 70%) of the LHRH-binding site from the membrane preparation. Ligand binding studies using LHRH analogues were carried out to determine dissociation constants for LHRH receptors both in situ in the membrane preparation and for solubilized LHRH receptors. For all the analogues the binding characteristics were similar in both preparations, suggesting that the solubilization procedure left the LHRH receptor undenatured. Gel filtration revealed an apparent molecular weight for the LHRH receptor of 100,000-160,000, with the mean value being approximately twice that found by others using sodium dodecyl sulphate-polyacrylamide gel electrophoretic techniques. The results indicate that the LHRH receptor probably exists in gonadotroph membranes as a large complex of more than one subunit.

Animals↗
PubMed1990

LHRH-receptors and LHRH-agonist treatment in ovarian cancer: an overview.

Considerable evidence exists that ovarian cancer might be gonadotrophin-dependent. Receptors for LH and FSH have been discovered in these tumors. Proliferation of ovarian cancer cells in vitro could be stimulated by gonadotrophins. Withdrawal of LH and FSH in animal models of ovarian cancer inhibited growth of these tumors. Phase-II clinical studies have shown that suppression of endogenous gonadotrophins by LHRH-agonists can be beneficial in women with advanced ovarian cancer. Respective controlled clinical trials are performed at present. Also direct effects of LHRH analogues on ovarian tumors have been reported. An LHRH like protein was found in human ovarian tissue. We discovered a specific LHRH binding site (mol. wt 63.2 kDa) in ovarian cancer tissue which is very similar to other human extrapituitary LHRH binding sites, of the low-affinity, high-capacity type, e.g. in breast cancer and the placenta. In the latter tissues, LHRH or a related substance has been proposed as an autocrine regulator of cellular function. If this was also the case in ovarian cancer, direct effects of LHRH analogs on the tumor cells could be used as additional therapeutical points of attack.

Animals↗
PubMed1985

Ovarian LHRH receptors increase following lesions of the major LHRH structures in the rat brain: involvement of a direct neural pathway.

Specific lesions of different brain structures known to contain or to be coursed by LHRH neurons have been carried out in intact cycling female rats in order to investigate the role played by central LHRH and neuronal systems in the regulation of ovarian and hypophyseal LHRH receptor (LHRH-R) levels, using the stable LHRH analog [D-Ser (TBU)6] Des-Gly10, LHRH ethylamide, buserelin. Radiofrequency lesions were placed bilaterally or unilaterally into female rats showing at least two consecutive estrous cycles, under pentobarbital anesthesia, while groups of animals were sham-operated. Bilateral lesions placed into the septal area and into the nucleus and tract of the diagonal band of Broca (DBB) resulted in a nearly 25-40% stimulation of LHRH binding activity within the ovaries and a 30% inhibition of LHRH analog binding to pituitary homogenate, while lesions placed into the medial preoptic area (MPO), where the majority of LHRH neurons are found, produced a doubling of ovarian LHRH-R accompanied by a 60% decrease of pituitary binding sites. Lesions involving the median eminence and arcuate hypothalamic nucleus, where the most conspicuous convergence of LHRH fibers occurs, produced a twofold increase in ovarian LHRH-R levels and an almost complete loss of pituitary LHRH-R binding capacity, with no change in affinity. In order to clarify the importance of direct neural signals modulating the ovarian LHRH-R concentration, lesions were placed in the right or left MPO and DBB, and the content of LHRH-R measured in right and left ovaries. Lesions placed unilaterally (right or left) produced a significant increase of LHRH-R binding activity within the ovary ipsilateral to the lesion, while a reduction or no effect was observed in the contralateral gland. Data show a marked stimulation of ovarian LHRH-R number following bilateral lesions placed in the major LHRH-containing structures, while pituitary LHRH binding sites are significantly inhibited, indicating impairment in the rate and/or amplitude of endogenous hypothalamic LHRH release. Furthermore results obtained following unilateral lesions indicate that a neural mechanism is involved in ovarian LHRH receptor induction and further reinforce our view that a direct neural connection links the brain and the ovaries.

Animals↗
PubMed2000

High incidence of receptors for luteinizing hormone-releasing hormone (LHRH) and LHRH receptor gene expression in human prostate cancers.

PURPOSE: Agonistic analogs of luteinizing hormone-releasing hormone (LHRH) are widely used for therapy of advanced prostate cancer based upon their ability to suppress testosterone secretion in patients. Various studies also indicate that LHRH analogs might have direct inhibitory effects on prostate tumors mediated by specific LHRH receptors. In this study we investigated the presence and characteristics of receptors for LHRH and their messenger (m) ribonucleic acid (RNA) expression in specimens of human prostate adenocarcinomas and benign prostatic tissue. MATERIALS AND METHODS: In vitro ligand competition assays as well as reverse transcriptase polymerase chain reaction (RT-PCR) were performed to investigate the expression of receptors for LHRH in surgical specimens of human prostate cancers and benign prostatic tissue. RESULTS: Sixty-nine of 80 (86%) cancers exhibited specific, medium to high-affinity binding for [D-Trp6]LHRH with a dissociation constant (Kd) of 6.55+/-0.4 nM and a maximal binding capacity (Bmax) of 483.6+/-25.4 fmol./mg. membrane protein. Two prostate cancer patients who were treated with the LHRH agonist goserelin prior to prostatectomy did not show tumor LHRH receptors. The expression of mRNA for LHRH receptors was observed in 19 of 22 (86%) prostate cancers. Benign prostatic tissue also displayed LHRH receptor gene expression, but exhibited lower Bmax value. There was a negative correlation (p <0.001) between LHRH receptor binding capacity and cancer grade (Gleason score); higher Gleason scores were associated with significantly lower binding capacity but an increased binding affinity. CONCLUSIONS: The expression of specific receptor proteins for LHRH in human prostate cancer provides a rationale for the improvement in methods for therapy of this malignancy based on LHRH analogs.

Aged↗
PubMed2002

Locally expressed LHRH receptors mediate the oncostatic and antimetastatic activity of LHRH agonists on melanoma cells.

Malignant melanoma is a tumor known for its uncontrollable growth and aggressive metastatic behavior. The mean survival time for patients with a metastatic melanoma is estimated to be less than 6 months, tumor cells being refractory to the conventional chemotherapy. A better understanding of the mechanisms regulating melanoma growth and progression might help increase the number of therapeutic options for this pathology. In this paper, we have shown that LHRH receptors are present in the BLM melanoma cell line, both at mRNA and at protein level; a potent LHRH agonist (LHRH-A; Zoladex) binds to these receptors with high affinity. BLM cells also express the mRNA for LHRH, indicating the presence of an autocrine LHRH-based system in melanoma cells. The treatment of BLM cells with LHRH-A dose-dependently inhibited cell proliferation; this effect was found to be specific because it was completely abrogated by the simultaneous treatment of the cells with a LHRH antagonist. Similar observations could be obtained in another melanoma cell line (Me15392). The activation of LHRH receptors, by means of LHRH-A, also reduced the ability of melanoma cells to invade a reconstituted basement membrane (Matrigel) and to migrate through a Boyden's chamber in response to a chemotactic stimulus. These data represent the first report that 1) LHRH and LHRH receptors are expressed in melanoma tumor cells; and 2) the activation of tumor LHRH receptors reduces both the proliferation and the metastatic potential of melanoma cells. It is suggested that the expression of LHRH receptors might represent a new diagnostic marker for the detection and progression of melanoma. These receptors might also be considered as a possible molecular target for a hormone-based therapeutic approach to this tumor.

Antineoplastic Agents, Hormonal↗
PubMed2004

Evidence for LHRH-receptor expression in human airway epithelial (Calu-3) cells and its role in the transport of an LHRH agonist.

PURPOSE: To determine whether LHRH-receptor is expressed in Calu-3, a human bronchial epithelial cell line, and to further determine whether this receptor plays a role in the transport of deslorelin, an LHRH agonist. METHODS: Using cultured monolayers of Calu-3 grown at air-interface, the presence and localization of LHRH-receptors in Calu-3 cells was determined using immunochemical methods. To determine the mechanisms of deslorelin transport, the directionality [apical-basolateral (A-B) and basolateral-apical (B-A)] of deslorelin transport across Calu-3 monolayers and the effects of temperature (37 degrees C and 4 degrees C) and an energy depletor (2,4-dinitrophenol) were investigated. To determine the role of LHRH-receptor in deslorelin transport across Calu-3 monolayers, the influence of an LHRH-receptor antisense oligonucleotide on the LHRH-receptor expression and deslorelin transport was studied. Also, the effect of a competing LHRH agonist, buserelin, on deslorelin transport was determined. RESULTS: Immunofluorescence studies indicated the predominance of LHRH-receptor in Calu-3 cells at the apical and lateral surfaces. Western blot and RT-PCR studies further confirmed the expression of LHRH-receptor in Calu-3 cells. Deslorelin transport across Calu-3 monolayers was vectorial, with the cumulative A-B transport (1.79 +/- 0.29%) at the end of 240 min being higher than the B-A transport (0.34 +/- 0.11%). Low temperature as well as 2,4-dinitrophenol abolished this directionality. LHRH-receptor antisense oligonucleotide decreased the receptor expression at the mRNA and protein level and reduced the A-B deslorelin transport by 55 +/- 4%, without affecting the B-A transport, suggesting a role for LHRH-receptor in the vectorial transport of deslorelin. In addition, buserelin reduced the A-B deslorelin transport by 56 +/- 5% without affecting the B-A transport. CONCLUSIONS: Taken together, our results provide evidence that deslorelin is transported across the respiratory epithelium via the LHRH-receptor.

2,4-Dinitrophenol↗
PubMed1996

Chronic administration of the luteinizing hormone-releasing hormone (LHRH) antagonist cetrorelix decreases gonadotrope responsiveness and pituitary LHRH receptor messenger ribonucleic acid levels in rats.

Continuous exposure to LHRH or its agonistic analogs results in a reduction of LHRH receptor sites and messenger RNA (mRNA) transcripts as well as in desensitization of the pituitary gonadotropes. To determine, whether LHRH antagonists might be similar in this respect to the agonists, we treated male rats for 4 weeks with daily sc injections of LHRH antagonist [Ac-D-Nal2,Phe(4Cl)2,D-Pal(3)3, D-Cit6,D-Ala10]LHRH (Cetrorelix acetate) or LHRH agonist, [D-Trp6]LHRH, in doses of 100 micrograms/animal-day. Another group of rats received a single im injection of 4.5 mg Cetrorelix pamoate depot, a sustained delivery formulation of the LHRH antagonist. An iv stimulation test with LHRH (200 ng/rat) was performed after 4 weeks of treatment. The rats were killed, and pituitary LHRH receptor characteristics were measured by RRA. To examine the effect of LHRH antagonist treatment on the expression of the pituitary LHRH receptor gene, some of the rats injected with Cetrorelix pamoate depot were killed after 2 weeks, and levels of LHRH receptor mRNA were determined by Northern blot and dot blot hybridization to a 32P-labeled rat complementary DNA probe. Our data show that LHRH-stimulated LH secretion at 30 min was suppressed by approximately 33% (P < 0.01) in rats pretreated with [D-Trp6]LHRH compared to that in animals injected with LHRH alone. Pretreatment of the rats with the LHRH antagonist suppressed the LH response to LHRH more markedly, the LH levels at 30 min were decreased by 89.8% and 96% in groups treated with Cetrorelix acetate and Cetrorelix pamoate depot, respectively. The testosterone response was virtually abolished in groups receiving Cetrorelix. The concentration of pituitary receptors for LHRH fell by 69% in the [D-Trp6]LHRH group, whereas the reductions in the Cetrorelix acetate group and in the group that received Cetrorelix pamoate depot were 77% and 82%, respectively. Treatment with Cetrorelix pamoate depot led to a 75-80% decrease in the levels of 5.0- and 4.5-kilobase forms of LHRH receptor mRNA compared to those in the control group. Dot blot analysis also showed 83% reduction in the mRNA for LHRH receptor. In conclusion, these data demonstrate that prolonged administration of LHRH antagonists such as Cetrorelix causes an impairment of gonadotropin secretion and a marked decrease in the levels of LHRH receptors as well as in the expression of the LHRH receptor gene. Thus, the down-regulation of pituitary LHRH receptors produced by LHRH antagonists appears to be similar to that resulting from the agonists.

Animals↗
PubMed1985

Changes in pituitary and ovarian LHRH receptors after active immunization of female rats against LH or LHRH.

The hypothalamic-pituitary-ovarian axis of female rats was disrupted at the site of LHRH stimulation by active immunization against LHRH or at the site of LH action by active immunization against LH. Active immunization against LH was associated with an increase in pituitary LHRH receptors to levels comparable to control values at pro-oestrus whereas immunization against LHRH led to a marked reduction in receptor numbers. Ovarian LHRH receptor concentrations were increased by both treatments. It is concluded, therefore, that (1) LHRH receptors in the pituitary and ovary are not concomitantly controlled, and (2) pituitary receptor numbers are primarily under positive autoregulatory control by LHRH and that ovarian LHRH receptor concentrations may be under long-term influence of LH.

Animals↗
PubMed1981

Dissociated changes of pituitary luteinizing hormone-releasing hormone (LHRH) receptors and responsiveness to the neurohormone induced by 17 beta-estradiol and LHRH in vivo in the rat.

A single injection of 17 beta-estradiol into castrated male or female rats results in an initial decrease in plasma concentrations of LH and pituitary responsiveness to LHRH, followed by a rapid return to normal or slightly elevated values. Under such experimental conditions, no acute change of binding of [125I-labeled D-Ser(TBU)6]LHRH ethylamide to anterior pituitary homogenate could be observed. Moreover, the self-priming effect of LHRH, as illustrated by a 10-fold increase in the LH response to a second injection of LHRH in the afternoon of proestrus, is accompanied by a 40% loss of pituitary LHRH receptors. During the estrous cycle, a 100% increase in pituitary LHRH receptors is already found on diestrus II, while the maximal LH responsiveness to LHRH occurs later, namely on the afternoon of proestrus. The present findings of a dissociation between changes in LHRH receptor levels and LH responsiveness to the neurohormone suggest that postreceptor events play a predominant role in the control of gonadotropin secretion by sex steroids and LHRH itself. Moreover, LHRH can cause an acute down-regulation of its own receptor in the anterior pituitary gland.

Animals↗
PubMed1985

Estradiol-induced LH release in juvenile female rats: nembutal blocks both the decline and the exposure of nonavailable pituitary LHRH receptor sites.

We have previously shown that, as seen in the adult rat, pituitary LHRH receptor content declines during the hours encompassing the first preovulatory LH surge. This decrease in receptor number was prevented, however, when pituitary membranes were treated with MgCl2 to dissociate endogenously bound ligand(s). The present study investigates: whether the first proestrous reduction in available LHRH receptors can be reversed by subjecting the pituitary membranes to a less drastic, dilution-washing procedure previously reported to be highly effective in dissociating bound LHRH, and whether Nembutal blockade of the proestrous decline in LHRH receptors also prevents the dissociation-induced exposure of additional LHRH binding sites. A premature LH surge was induced by exposing juvenile female rats to proestrous-type levels of plasma estradiol (E2) via Silastic capsules. A decline in available LHRH receptors was found around the time of this steroid-induced LH surge. A marked increase in receptor number was, however, observed upon dilution-washing of the membranes. The increase in receptor number was not accompanied by any changes in receptor affinity (ka). Nembutal administration blocked both the LH surge and the decline in available LHRH receptors. Moreover, dilution-washing of pituitary membranes from Nembutal-treated rats failed to uncover additional LHRH binding sites. The results suggest that a significant portion of the proestrous decline in pituitary LHRH receptors is due to a reduced availability of the receptor to binding. Whether such a phenomenon is due to true occupancy by endogenous ligand(s) or to binding-dependent localization of the receptor within the cell membrane is unclear.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Basal and stimulated LHRH receptor sites in the pituitary of aging female mice.

We studied the regulation of pituitary luteinizing hormone-releasing hormone (LHRH) receptors in female mice aged 4-8 months (young), 10-14 months (middle-aged) and 15-18 months (old). In intact animals the mean +/- SE pituitary content of LHRH receptor sites ranged from 34.4 +/- 6.3 fmoles to 41.5 +/- 5.0 fmoles and remained constant throughout aging. Similarly, receptor affinity for LHRH was unaltered (range 1.0-4.0 X 10(9) M-1) by age. Ovariectomy (ovx) resulted in a 30-50% decrease in pituitary LHRH receptor sites (p less than 0.05) and the pattern of LHRH receptor fall after ovx was similar in all three age groups. Administration of estrogens (E2) at either a low (0.2 mg) or a high (2.0 mg) concentration to ovx mice prevented this fall in LHRH receptor sites and, in all three age groups, increased pituitary values to levels comparable to those measured in intact animals. We conclude that there are no significant differences in the basal and stimulated number or affinity of pituitary LHRH receptors between young, middle-aged and aged female mice.

Aging↗
PubMedDate not supplied

Modulation of hippocampal LHRH receptors by sex steroids in the rat.

The modulation of brain LHRH receptors by sex steroids was assessed in the female rat hippocampus using in vitro autoradiography and iodinated [D-Ser (TBU)6, des-Gly-NH2(10)]LHRH ethylamide as the radioligand. As evaluated by optical densitometry, the density of hippocampal LHRH receptors was increased by castration. In castrated animals, estradiol administration produced a small decrease in receptor concentration, whereas the concomitant administration of progesterone and estradiol as well as the injection of dihydrotestosterone induced a marked decrease in receptor density. Progesterone administration did not produce any significant change in receptor concentration. These results indicate that brain LHRH receptors can be modulated by sex steroids. Interestingly, this modulation of hippocampal LHRH receptors is similar to that previously observed in pituitary gland.

Animals↗
PubMed1987

Characterization and autoradiographic localization of LHRH receptors in the rat brain.

Luteinizing-hormone-releasing hormone (LHRH) is distributed in several extrahypothalamic areas, suggesting that it might act as a neurotransmitter or neuromodulator in the central nervous system. This study was undertaken to characterize and localize LHRH receptors in the rat brain by using slide-mounted frozen sections. The radioligand used was an iodinated stable LHRH agonist, [D-Ser(TBU)6, des-Gly-NH2(10)]LHRH ethylamide. It was clearly established that LHRH receptors with characteristics similar to those of pituitary LHRH receptors were present in the brain. They were found in high concentrations in the dorsal hippocampus, amygdala, septum, and subiculum and in very low amounts in the hypothalamus. Generally, a good correlation could be observed between receptor distribution and immunohistologically localized LHRH. These results strongly suggest that LHRH has multiple sites of action in the rat brain and reinforce the hypothesis that the peptide could act as a neurotransmitter/neuromodulator in the central nervous system.

Animals↗
PubMed1983

Peripubertal decline in ovarian LHRH receptor content: characterization and distribution.

In the rat, ovarian LHRH receptor content, as measured by the binding of 125I-D-Ala6, Pro9-LHRH (A-LHRH) to ovarian membranes, decreases markedly during the days preceding the first preovulatory gonadotropin surge. The present study shows that the decrease in LHRH receptor number occurs exclusively in granulosa cells, and that the greatest rate of decline takes place between the juvenile period and the early proestrous phase of puberty. In contrast to granulosa cells, membranes prepared from ovarian tissues after removal of these cells demonstrated no significant change in LHRH binding capacity throughout puberty. Scatchard analysis of competition curves, constructed using membranes from whole ovaries, revealed that receptor affinity remains unchanged (Ka = 9 X 10(9) M-1) as the receptor number decreases. Kinetic binding studies demonstrated that LHRH binding to its receptor reaches equilibrium within 40 min and can be displaced by addition of unlabeled hormone. A kinetic estimate of receptor affinity provided values similar to those obtained by Scatchard analysis. Treatment of ovarian membranes with MgCl2 to uncover occupied binding sites results in more than 70% dissociation of bound labeled ligand. Dissociation of endogenous LHRH using this procedure resulted in some increase in available binding sites only in juvenile rats, but not in first proestrous or first estrous animals in which receptor content was low. The results demonstrate that the decline in ovarian LHRH receptors observed during peripubertal days is confined to granulosa cells, is not due to changes in receptor affinity, and represents a true loss of binding sites.

Animals↗