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Inhibition of adenylate cyclase from luteinized rat ovary by monovalent cations: roles of the stimulatory guanine nucleotide-binding regulatory component and stimulatory hormone receptor.

Sodium and other monovalent cations (added as chloride salts) inhibited adenylate cyclase of luteinized rat ovary. Sodium chloride (150 mM) inhibited basal enzyme activity by 20%. Sodium chloride inhibition was enhanced to 34-54% under conditions of enzyme stimulation by guanine nucleotides (GTP and its nonhydrolyzable analog 5'-guanylyl imidodiphosphate), fluoride anion, and agonists (ovine luteinizing hormone (oLH) and the beta-adrenergic catecholamine isoproterenol) acting at stimulatory receptors linked to adenylate cyclase. Sodium chloride inhibition was dependent on salt concentration over a wide range (25-800 mM) as well as the concentrations of GTP and oLH. Inhibition by NaCl was of rapid onset and appeared to be reversible. The order of inhibitory potency of monovalent cations was Li+ greater than Na+ greater than K+. The role of individual components of adenylate cyclase in the inhibitory action of monovalent cations was examined. Exotoxins of Vibrio cholerae and Bordetella pertussis were used to determine respectively the involvement of the stimulatory and inhibitory guanine nucleotide-binding regulatory components (Ns and Ni) in NaCl inhibition. Sodium chloride inhibited cholera toxin-activated adenylate cyclase activity by 29%. Ni did not appear to mediate cation inhibition of adenylate cyclase because pertussis toxin did not attenuate inhibition by NaCl. Enzyme stimulation by agents (forskolin and Mn2+) thought to activate the catalytic component directly was not inhibited by NaCl but was instead significantly enhanced. Sodium chloride (150 mM) increased both the Kd for high-affinity binding of oLH to 125I-human chorionic gonadotropin binding sites and the Kact for oLH stimulation of adenylate cyclase by sevenfold. In contrast, NaCl had no appreciable effect on either isoproterenol binding to (-)-[125I]iodopindolol binding sites or the Kact for isoproterenol stimulation of adenylate cyclase. The results suggest that in luteinized rat ovary monovalent cations uncouple, or dissociate, Ns from the catalytic component and, in a distinct action, reduce gonadotropin receptor affinity for hormone. Dissociation of the inhibitory influence of Ni from direct catalytic activation could account for NaCl enhancement of forskolin- and Mn2+-associated activities. On the basis of these results, the spectrum of divergent stimulatory and inhibitory effects of monovalent cations on adenylate cyclase activities in a variety of tissues may be interpreted in terms of differential enzyme susceptibilities to cation-induced uncoupling of N and catalytic component functions.

Adenylyl Cyclase Inhibitors↗

Expression and alternative splicing of the neural cell adhesion molecule NCAM in human granulosa cells during luteinization.

Freshly aspirated human granulosa cells from pre-ovulatory follicles and granulosa cells luteinized in culture possess the neural cell adhesion molecule (NCAM) of approximate molecular mass of 140,000 and NCAM mRNA as confirmed by S1-nuclease protection assays and RT-PCR. Moreover, in the process of luteinization the NCAM isoform pattern is modified. Isoforms containing an insert of 10 amino acids (termed VASE) in the extracellular domain of NCAM were supplemented by alternatively spliced isoforms without this insert. NCAM immunoreactivity, at light and electron microscope levels, was associated with the cell membrane of most granulosa cells which formed clusters. During time in culture an increasing subpopulation of granulosa cells, devoid of NCAM immunoreactivity, spread out and formed monolayers. This differential expression and the alternative splicing of NCAM during luteinization of granulosa cells raise the possibility that NCAM could be involved in folliculogenesis and the formation of the corpus luteum in the human.

Alternative Splicing↗

Ovarian malignant luteinized thecoma--an unusual tumor in an adolescent.

Malignant luteinized thecoma is an extremely rare ovarian tumor. The fifth reported case of this tumor presenting in a 13-year-old epileptic child on anticonvulsant therapy with a rapidly enlarging pelvic-abdominal mass is discussed. At laparotomy, bilateral ovarian involvement, massive ascites, and omental and bowel serosal metastases were present. The pathological diagnosis was difficult with initial diagnoses of ovarian edema, endodermal sinus tumor, and ovarian fibrosarcoma. The final diagnosis of malignant luteinized thecoma was made by recognizing the presence of lutein cells with foamy vacuolated cytoplasm and intracytoplasmic staining for oil red O. Electron microscopy also demonstrated vacuolated cells with multiple fat globules. After surgical debulking the patient was treated with combination chemotherapy with complete response. The similarities of this case to three previously reported bilateral thecomas presenting in children on anticonvulsant therapy is discussed.

Adolescent↗

A comparison of hormone levels in follicle-lutein-cysts and in normal bovine ovarian follicles.

Insulin-like growth factors 1 and 2 (IGF-1 and 2), oxytocin, progesterone, estradiol and ubiquitin were measured in bovine follicle-lutein-cysts and in follicular fluid after the classification of ovarian follicles by size (Class I = <4 mm; Class II = 5-8 mm; Class III = 9-12 mm; Class IV = preovulatory; Class V = cystic). It was found that IGF-1 concentrations increased during growth from 280 ng/ml in small follicles to 489 ng/ml in preovulatory follicles; IGF-2 appeared to remain constant in follicular fluid and in cysts (275 ng/ml). Oxytocin values were low in Class I, II and III follicles (30 pg/ml) but increased in preovulatory and cystic follicles (75 pg/ml). Estradiol increased significantly only in preovulatory follicles. Ubiquitin, a protein reflecting cellular replicative activity, could be found in bovine follicular fluid in high concentrations: 1.6 mug/ml in Class I,II and III follicles with the highest amounts in preovulatory follicles (2.3 mug/ml). In contrast with normal follicles, cysts were found to have a minimal concentration of ubiquitin (0.3 mug/ml). Progesterone levels were 5 times higher in cysts (325 ng/ml) and IGF-1 concentrations were markedly higher in cystic follicles (881 ng/ml) than in the other follicles. Simultaneously, maximum gene expression for IGF-1 was found in granulosa/lutein cells of cystic follicles (Class V), suggesting de novo synthesis of IGF-1. Between the different follicle classes progesterone, oxytocin and IGF-1 concentrations correlated positively (r=0.82). Hormonal levels in follicle-lutein-cysts indicated an arrested stage of insufficient luteinization as a possible result from the premature release of LH or from the release of amounts of LH inadequate to cause ovulation.

Journal Article↗

Expression and regulation of luteinizing hormone/human chorionic gonadotropin receptors in ovarian cancer and its correlation to human chorionic gonadotropin-doxorubicin sensitivity.

OBJECTIVE: Ovarian cancer cell lines and tissues express gonadotropin receptors. Conjugation of cytostatics to ligands of these receptors may increase the specificity of cytotoxic drugs. STUDY DESIGN: Toxicity of doxorubicin-human chorionic gonadotropin conjugates was determined in 4 ovarian cancer cell lines. Expression and regulation of luteinizing hormone/human chorionic gonadotropin receptors were analyzed before and after treatment with human chorionic gonadotropin, epidermal growth factor, and 8-bromo-cyclic adenosine monophosphate with a nested reverse transcriptase-polymerase chain reaction approach. RESULTS: Toxicity of human chorionic gonadotropin-doxorubicin conjugates was increased compared with unconjugated doxorubicin in OVCAR-3 cells. However, drug conjugates failed to demonstrate increased toxicity in other cell lines, especially after preincubation with human chorionic gonadotropin. All cell lines expressed luteinizing hormone/human chorionic gonadotropin receptors. Receptor expression in OVCAR-3 cells was not effected by human chorionic gonadotropin, endothelial growth factor, or 8-bromo-cyclic adenosine monophosphate treatment. In other cell lines, receptor expression was down-regulated by these agents. CONCLUSION: Cytotoxic activity of doxorubicin was increased specifically by conjugation to human chorionic gonadotropin. However, the regulation of luteinizing hormone/human chorionic gonadotropin receptor expression and other compounds may reduce the drug-uptake of the conjugates.

Antibiotics, Antineoplastic↗

Ovarian luteinized thecoma with sclerosing peritonitis in an adult woman treated with leuprolide and toremifene in complete remission at 5 years.

BACKGROUND: Luteinized thecoma of the ovary associated with sclerosing peritonitis is a rare pathologic condition without a standard strategy of treatment. CASE: We present the case of an ovarian luteinizing sclerosing thecoma in a 39-year-old woman. The patient underwent three laparotomic operations for subocclusive symptoms, revealing in both occasions the presence of sclerosing peritonitis, with large abdominal masses, including cysts containing clear fluid. Treatment with toremifene 20 mg/day and leuprolide resulted in a dramatic improvement of the performance status and complete remission of all the abdominal lesions. After 60 months follow-up, the patient is still disease-free. DISCUSSION: Antiestrogens plus LHRH agonists might be a noninvasive, effective and well-tolerated therapy for sclerosing peritonitis in patient operated for luteinized thecomas.

Adult↗

Ultrasonic evidence for luteinization of unruptured preovulatory follicles.

Luteinization of an unruptured ovarian follicle has been reported as a cause of infertility and has heretofore been diagnosed only by direct visualization of the ovarian surface. Four patients who demonstrated defects in ovulation requiring therapy to induce ovulation and who were not achieving desired conception despite apparently adequate treatment were studied with serial pelvic ultrasonic examinations for 17 cycles. Luteinization, characterized by the loss of a clear demarcation of the follicular cyst wall and the presence of intrafollicular echoes, was suspected in each of these cycles by the absence of ultrasonic signs of ovulation--that is, a rapid decrease in follicular size and the appearance of free fluid in the cul-de-sac. Histologic confirmation of a persistent luteinized cyst is presented.

Chorionic Gonadotropin↗

Effects of melatonin on progesterone production by human granulosa lutein cells in culture.

OBJECTIVE: To test the hypothesis that melatonin modulates steroid synthesis in the human ovary. DESIGN: Granulosa lutein cells obtained from in vitro fertilization cycles were cultured in medium containing melatonin and human chorionic gonadotropin (hCG). RESULTS: Progesterone (P) secretion by granulosa lutein cells increased progressively in both basal and hCG-stimulated conditions, up to 96 hours in culture, plateaued at 144 and decreased thereafter. Melatonin (10(-7), 10(-9), 10(-11) M) had no effect on basal P or 17 beta-estradiol production. The addition of melatonin to the hCG-treated granulosa lutein cells significantly (P less than 0.05) potentiated the stimulatory effect of hCG on P production. The effect was most prominent after 144 and 196 hours of incubation. CONCLUSION: This observation suggests a role for melatonin in the intraovarian control of P production in the human ovary.

Cells, Cultured↗

Leuprolide acetate: serum and follicular fluid concentrations and effects on human fertilization, embryo growth, and granulosa-lutein cell progesterone accumulation in vitro.

Data from various animal models have demonstrated significant extrapituitary effects of gonadotropin-releasing hormone agonists. The purpose of this study was to determine the effects of therapeutic concentrations of leuprolide acetate on human granulosa-lutein cell steroidogenesis, fertilization, and embryo growth rates in vitro. During leuprolide administration, mean serum concentrations of leuprolide were less than 50 ng/ml and were undetectable 48 hours after cessation of administration. There was no effect of leuprolide on progesterone (P) secretion by granulosa-lutein cells cultured in the presence or absence of human chorionic gonadotropin. The effect of leuprolide on embryo growth rates was evaluated with the mouse two-cell embryo culture model and a retrospective review of early embryo growth rates in humans receiving adjunctive leuprolide therapy. There was no measurable effect of leuprolide on early embryo growth in either species. These data indicate that (1) serum and follicular and peritoneal fluid concentrations are undetectable 2 days after discontinuation of leuprolide; (2) there is no measurable effect of leuprolide on human or murine embryo growth rates up to the 8 cell stage in vitro; and (3) there is no measurable effect of leuprolide on granulosa-lutein cell P accumulation.

Animals↗

Sudden death due to disease flare with luteinizing hormone-releasing hormone agonist therapy for carcinoma of the prostate.

Luteinizing hormone-releasing hormone agonist therapy for prostate cancer is a new method of management for metastatic disease. During the initial 1 to 2-week period of administration an increase in serum testosterone concentration can lead to an exacerbation of clinical symptoms (flare phenomenon). Two patients are summarized who received luteinizing hormone-releasing hormone agonist therapy without flare blockade and died suddenly during month 1 of therapy. A review of 765 patients in 9 series found 10.9% who suffered disease flare and 15 who died during disease flare. Of these 17 patients 12 were similar to our 2. These data suggest that any patient placed on luteinizing hormone-releasing hormone agonist therapy for prostate cancer merits some form of flare blockade during the initial 1 or 2 months of therapy.

Adenocarcinoma↗

Age-related changes in the suppression of serum luteinizing hormone by estradiol-17beta in developing steers.

Serum luteinizing hormone (LH) concentrations were measured at 4, 6, 8 and 10 mo of age in estradiol-17beta (E(2))-treated (n = 4) and contemporary control steers (n = 4). Serum LH was measured in samples collected at 30-min intervals starting at 0600 h for 12 h and for an additional 6 h following luteinizing hormone-releasing hormone (LHRH) injection. Estradiol-17beta suppressed mean serum LH concentrations at all ages (P<0.01), but it suppressed pulsatile release of LH only at 4 and 6 mo (P<0.01), not 8 and 10 mo of age. Luteinizing hormone release in response to LHRH, expressed as the area under the secretory curve, was larger and LH concentrations returned to pre-LHRH levels later in E(2)-treated steers (P<0.01). Peak LH concentrations after LHRH varied with age (P<0.05) but not E(2) treatment. These results suggest that E(2) suppression of LH in steers occurs at the hypothalamic level and developmental changes take place within the hypothalamicpituitary axis in absence of androgen feedback from the testis.

Journal Article↗

Regulation of PKC delta expression by estrogen and rat placental lactogen-1 in luteinized rat ovarian granulosa cells.

Protein kinase C (PKC) delta is dramatically upregulated in the corpus luteum in the second half of pregnancy in the rat. To gain insight into the hormonal regulation of PKC delta expression, studies were undertaken to analyze the regulation of PKC delta expression in a luteinized rat granulosa cell model. PKC delta protein expression was evaluated in luteinized granulosa cells, isolated from human (h)CG-treated immature female rats 7 h after the injection of an ovulatory dose of hCG and cultured up to 12 days. Cytochrome P450 cholesterol side chain cleavage enzyme expression was observed throughout the culture period, and a majority of the cells expressed steroidogenic acute regulatory protein and responded to rat placental lactogen (rPL)-1 by exhibiting hypertrophy, consistent with maintenance of the luteal phenotype. Both PKC delta protein and mRNA expression increased 3.5-4-fold with time of culture, and PKC delta mRNA expression could be eliminated by treatment of cells with the PKC inhibitor GF109203X. E(2) caused a specific dose- and time-dependent increase in expression of PKC delta protein of twofold, whereas PKC delta mRNA was unaffected by E(2) over a 12-day culture period. Treatment of cells with 500 ng/ml rPL-1 for the final 4 days of a 12-day culture in the absence of E(2) had no effect on PKC delta protein or mRNA expression, while treatment with 500 or 3000 ng/ml rPL-1 in the presence of E(2) significantly enhanced both PKC delta protein and mRNA expression (up to threefold). These results show that two of the major regulators of luteal function in the second half of pregnancy in the rat, E(2) and rPL-1, cooperate to regulate PKC delta expression in luteinized granulosa cells.

Animals↗

Modulatory action of epidermal growth factor on differentiated human granulosa lutein cells: cross-talk between ligand activated receptors for EGF and gonadotropin.

A number of local regulatory factors including polypeptide growth factors like epidermal growth factor (EGF) have been suggested to play an active role within the human ovary. In order to understand the physiology of EGFs action, it is essential to demonstrate and characterize the receptors for this growth factor on ovarian cells which was the aim of this study. We demonstrate using [125I]EGF that specific high affinity sites with Ka for this ligand reaching 2.2 x 10(-9) M for growing cultures of human granulosa-lutein cells and 0.13 x 10(-9) M for the membrane fraction prepared from these cells. Additionally we have identified a 170 kD protein as the EGF receptor with the help of affinity cross linking and immunoblotting procedures. Furthermore, we observed that a pretreatment of granulosa lutein cells with EGF for a short duration (0-30 min) leads to a dose- and time dependent upregulation of the LH-receptor-coupled adenylate cyclase activity. A maximal effect (159 +/- 12% increase compared with untreated cells, P < 0.001, n = 4) was reached at 10-15 min with 10-20 ng/ml EGF. Specific inhibition of the receptor tyrosine kinase activity abolished the observed EGF-induced sensitization of the cyclase activity. Differentiation of granulosa cells in vivo is a prerequisite for ovulation and later transformation into highly differentiated lutein cells, a process depending on the presence of ligands that elevate cAMP production. The observed modulation of the adenylate cyclase by EGF could be a regulatory component for the differentiated status of the granulosa cells during different phases of the cycle.

Adenylyl Cyclases↗

Xanthophyll cycle-dependent nonphotochemical quenching in Photosystem II: Mechanistic insights gained from Arabidopsis thaliana L. mutants that lack violaxanthin deepoxidase activity and/or lutein.

This study compares Photosystem II (PS II) chlorophyll (Chl) a fluorescence yield changes of Arabidopsis thaliana L. nuclear gene mutants, thoughtfully provided by the authors of Pogson et al. (1998 Proc Natl Acad Sci USA 95: 13324-13329). One single mutant (npq1) inhibits the violaxanthin deepoxidase that converts violaxanthin to antheraxanthin and zeaxanthin. A second single mutant (lut2) inhibits the in-cyclization enzyme step between lycopene and beta,in-carotene causing accumulation of beta,beta-carotene derivatives, primarily the violaxanthin cycle pigments, at the expense of lutein. The double mutant (lut2-npq1) incorporates both lesions. PS II Chl a fluorescence was characterized in leaves and thylakoids using both steady state and time-resolved methods, the intrathylakoid pH was estimated by 9-aminoacridine fluorescence quenching and chloroplast pigments were determined by HPLC. Under maximal PS II Chl a fluorescence intensity conditions without intrathylakoid acidification, the main 2 nanosecond (ns) fluorescence lifetime distribution mode parameters were similar for the WT and mutants both before and after illumination. The light and ATPase mediated intrathylakoid pH levels were also similar and caused similar changes in the fluorescence lifetime distribution widths and centers for the WT and each mutant. The npq1 exhibited low antheraxanthin and zeaxanthin and high violaxanthin levels and the uncoupler-sensitive amplitudes of short (< 1 ns) PS II Chl a fluorescence distribution modes were strongly inhibited compared to the WT. Lutein deficiency coincided with pleiotropic effects on PS II energy dissipation and probably altered conformations of PS II carotenoid-chlorophyll binding proteins. The lut2 exhibited separate active and inactive pools of antheraxanthin and zeaxanthin with respect to all deepoxidation, epoxidation and fluorescence quenching activities. The active xanthophyll cycle pool in lut2 exhibited a lower ( approximately 35% of WT) concentration efficiency, for a given intrathylakoid pH, to increase the sub-nanosecond distribution amplitudes, which predicts and explains inhibited induction kinetics and fluorescence quenching. The lut2-npq1 mutant exhibited a constant pool of antheraxanthin and zeaxanthin, no deepoxidation and little or no pH-reversible fluorescence decrease. It is concluded that in addition to intrathylakoid acidification, a certain level of zeaxanthin and antheraxanthin (or lutein) is absolutely required for the major reversible component of PS II Chl a fluorescence quenching.

Journal Article↗

Recurrent bilateral theca lutein cysts in association with normal pregnancy.

We describe a case of a 28-year-old Saudi patient, gravida 6, para 5, at 14 weeks' gestation, who had recurrent bilateral theca lutein cysts during her last three pregnancies. The cysts were treated surgically during her fourth pregnancy because of acute abdomen at 20 weeks' gestation. Ovarian biopsy confirmed the diagnosis of theca lutein cysts and her pregnancy continued until term. In the last two pregnancies, the theca lutein cysts were managed conservatively by serial ultrasound examination and they resolved spontaneously. There was no history of molar pregnancy or use of ovulation-inducing drugs. The possibility that there was increased sensitivity of the ovarian tissue to human chorionic gonadotropin is discussed.

Adult↗

Leptin inhibits steroid biosynthesis by human granulosa-lutein cells.

Absence of leptin secretion compromises reproductive function and fertility in the ob/ob mouse which, when given leptin, shows a rise in serum LH levels and becomes fertile. Recently, the long and active isoform of the leptin receptor was detected in the ovary, indicating that leptin may also show direct gonad-related activity. To examine this, we studied the effect of graded doses of human leptin on estradiol (E2) and progesterone (P4) concentrations in the culture media of human granulosa-lutein cells obtained from follicular fluid of women undergoing in vitro fertilization. We also evaluated the mRNA expression of steroidogenic acute regulatory protein (StAR), aromatase, and cytochrome P450 17alpha (CYP17) in these cells at baseline and after exposure to leptin. Estradiol levels were significantly decreased in the media 24 hours after incubation of the cells with increasing hLeptin concentrations (10(-11) - 10(-7) mol/l). The maximal 30% decrease in E2 production was caused by the 10(-9) mol/l hLeptin concentration; however, P4 levels in the media were not influenced by leptin. Exposure of granulosa-lutein cells to 10(-9) mol/l hLeptin did not produce any measurable changes on StAR, aromatase, or CYP17 mRNA expression. When hLeptin (10(-9) mol/l) was co-incubated with increasing concentrations of hCG (1.25 - 10 mlU/ml), IGF-II (15-60 ng/ml) or 1-6 desaminated IGF-II (deslGF-II; 15-60 ng/ml), it did not modify the elevation of E2 concentrations caused by each of the different stimuli. We conclude that leptin suppresses E2 secretion by human granulosa-lutein cells but does not impair the stimulatory effects of hCG and IGFs on these cells. Leptin may play a minor, but direct regulatory role on unstimulated human ovarian steroidogenesis by interfering with either the translational or post-translational steps of the baseline CYP17 and/or aromatase synthesis and/or the activation of the enzymes.

Adult↗

Bovine granulosa cells express extracellular matrix proteins and their regulators during luteinization in culture.

This study investigated the ability of bovine granulosa cells to express and secrete collagen, metalloproteinase (MMP) activity and a tissue inhibitor of metalloproteinase (TIMP-1) during luteinization in vitro. Cells from mature (1-2 mL fluid volume) bovine follicles were cultured over 4 days in serum-free medium. Their luteinization during culture was confirmed by a 10-fold increase in progesterone secretion. Samples of cell extracts, culture media and follicular fluid were subjected to Western blotting to identify secreted proteins and to gelatin zymography to detect enzyme activity. Poly A+ RNA, isolated from cells before and after culture, was probed to detect expression of collagen alpha 1(I), collagen alpha 3(IV) and TIMP-1. The results revealed that: (1) the collagen alpha 1(I) subunit gene was expressed in cells before culture but with greater intensity by Day 4 culture; collagen I protein, on the other hand, was not detectable in culture medium; (2) the collagen alpha 3(IV) subunit gene was expressed at a low level in uncultured cells and could be detected on Day 4 of culture; low amounts of the protein were detected in medium; (3) a 92-kDa band of gelatinase activity (presumed MMP-9) was present in all medium samples, together with bands of unidentified activity; and (5) the TIMP-1 gene was expressed in uncultured cells but its expression increased markedly up to Day 4 of culture. These results show that granulosa luteinization is associated with an increase in the expression of collagen, collagen-degrading enzymes and TIMP-1. Collagen protein, however, may be only poorly synthesized in this culture model. The results suggest that granulosa-derived cells are a likely source of components of the extracellular matrix during post-ovulatory remodelling of early luteal tissue.

Animals↗

Similar luteinizing hormone-releasing hormone binding sites in rat anterior pituitary and ovary.

To study the luteinizing hormone-releasing hormone (LH-RH; luliberin) receptors in the rat anterior pituitary gland and ovary, 125I-labeled [D-Ser(TBU)6des-Gly-NH2(10)]LH-RH ethylamide was used as a labeled ligand. The binding characteristics were assessed by Scatchard analysis of labeled ligand binding and by potency displacement with unlabeled peptides. Similar Kd values, ranging from 0.1 to 0.3 nM, were found for the labeled and unlabeled peptides in both tissues. A similar order of potency was observed between the finding affinity of 15 peptides in anterior pituitary and ovarian homogenates and their biological activity on luteinizing hormone release in rat anterior pituitary cells in culture. These data demonstrate that the LH-RH receptors present in the rat ovary have a specificity similar to that of the anterior pituitary LH-RH receptor controlling secretion of luteinizing hormone and follicle-stimulating hormone. Moreover, the binding affinities of the LH-RH agonists and antagonists can account, at least up to a large extent, for their relative biological potencies. Although there definitely are specific LH-RH receptors in the ovary which may play a role in the antifertility effects observed after administration of LH-RH agonists, the possible physiological significance of these ovarian receptors is still unknown and of great biological interest.

Animals↗