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Interaction between glutamate and luteinizing hormone-releasing hormone (LHRH) in lordosis behavior and luteinizing hormone release (LH): further studies on NMDA receptor mediation.

The present studies examine the effects of the glutamate agonist N-Methyl-D-Aspartic acid on lordosis responsiveness and LH release in estrogen-primed, ovariectomized rats. Groups of rats previously cannulated in the 3rd ventricle of the brain (IVT) were challenged with saline, NMDA and LHRH. A clear increase in lordosis-to-mount quotients (LQ) after IVT administration of 0.5, 0.75 and 1 microgram NMDA was found. LHRH (150 ng IVT) also enhanced LQ. High plasma LH levels were present in both cases. Intraventricular administration of the selective LHRH antagonist [D-p-Glu1, D-Phe2, D-Trp3,6]-LHRH (100 ng) was unable to prevent NMDA action on lordosis behavior. In contrast, it blunted LHRH enhancement of LQ. LH release evoked by either NMDA and LHRH was blocked by the LHRH antagonist. Present results support our previous view suggesting that glutamate, through NMDA receptors, participates in the regulation of lordosis behavior. Glutamate seems to exert its actions in the behavioral and endocrine patterns through different mechanisms; the first seems not to be mediated by LHRH, but the endocrine effect operates via LHRH release.

Animals↗

Interactions between neuropeptide Y, luteinizing hormone-releasing hormone and estradiol in the control of luteinizing hormone release from cultured ovine pituitary cells.

This study used pituitary cells in culture firstly to test the hypothesis that NPY may augment the pituitary LH response to LHRH and secondly to determine whether this interaction is dependent on the presence of estradiol. LHRH (10(-10)-10(-6) M) caused a significant increase in LH secretion from dispersed ovine pituitary cells maintained in culture for six days, a response which was enhanced when cells were pretreated for three days with 4 x 10(-11) M estradiol. NPY 10(-10)-10(-6) M) had no effect on basal LH release from ovine pituitary cells maintained either in the presence or absence of estradiol. NPY (10(-10) and 10(-8) M) also had no effect on LHRH-stimulated LH release either in the presence or absence of estradiol. These results substantiate previous observations that physiologically relevant concentrations of estradiol enhance the LH response to LHRH in cultured ovine pituitary cells. However, in contrast to experiments carried out using rat pituitary cells in culture, the present data provide no evidence to support the hypothesis that NPY alone interacts with LHRH in the control of LH secretion from the ovine pituitary gland.

Animals↗

Follicular phase serum levels of luteinizing hormone do not influence delivery rates in in vitro fertilization cycles down-regulated with a gonadotropin-releasing hormone agonist and stimulated with recombinant follicle-stimulating hormone.

OBJECTIVE: To assess the value of serum LH measurements in early and late follicular phase as predictors of ovarian response and IVF outcome in patients treated with recombinant FSH with GnRH agonist (GnRH-a) pituitary down-regulation. DESIGN: Retrospective cohort analysis. SETTING: Institutional. PATIENT(S): Women undergoing 157 consecutive IVF cycles suppressed with leuprolide acetate (LA) started in the midluteal phase and stimulated with recombinant FSH. Only women <40 years of age and with a basal cycle day 3 serum FSH </=9 IU/L were included. INTERVENTION(S): Serum LH levels were measured on cycle days 3 (D3) and 10 (D10). MAIN OUTCOME MEASURE(S): Delivery rates. Other secondary outcome measures included fertilization rate, clinical pregnancy rate, and parameters of ovarian response (peak E(2), number of metaphase II oocytes, and number of ampules of recombinant FSH). RESULTS: No significant differences were found with respect to ovarian response, fertilization rate, and outcome of pregnancy, when three threshold values of D3 and D10 serum LH (1, 1.5, and 2 mIU/mL) were analyzed. In addition, no significant differences were found between conception (n = 87) and no conception (n = 71) groups with respect to D3 or D10 LH. Receiver operator characteristic (ROC) analysis showed that neither the serum LH concentration on D3 nor on D10 was able to discriminate between conception and nonconception cycles (area under the curve [AUC](ROC)= 0.54, AUC(ROC)= 0.56), or between delivered pregnancies and first trimester pregnancy loss (AUC(ROC)= 0.53, AUC(ROC) = 0.61). CONCLUSIONS: The suppressed levels of early and late follicular serum LH in women <40 years of age with normal ovarian function desensitized with a GnRH-a and treated with recombinant FSH are not predictive of ovarian response, pregnancy, or delivery. These data do not support the use of exogenous LH supplementation in this clinical scenario.

Adult↗

Luteinizing hormone increases estradiol secretion but has no effect on progesterone concentrations in the late follicular phase of in vitro fertilization cycles in women treated with gonadotropin-releasing hormone agonist and follicle-stimulating hormone.

OBJECTIVE: To determine whether the late follicular phase increase in circulating P concentrations during controlled ovarian stimulation with GnRH-a and FSH can be influenced by addition of LH to the stimulating gonadotropin during the final 2 days. DESIGN: Randomization of patients to receive either FSH alone or FSH with LH (hMG) for the final 2 days before hCG, after follicular phase stimulation with purified FSH. SETTING: A.C.S. Unit at the Royal Infirmary, Glasgow, U.K. PATIENT(S): Patients were unselected and were undergoing IVF. INTERVENTION(S): Patients received stimulation with purified FSH (300 IU/d) until a follicle of 15 mm was observed; the regimen was then changed to either 225 IU of FSH or 225 IU of hMG. MAIN OUTCOME MEASURE(S): Estradiol and P in the peripheral circulation. RESULT(S): Significant increases in E2 concentration were observed, but there were no changes in the circulating progesterone. CONCLUSION(S): The late follicular phase increase in P is unrelated to any luteinizing process attributable to effects in the circulation or sensitization of follicular cells to LH.

Adult↗

Peripheral plasma levels of luteinizing hormone-releasing hormone-like immunoreactivity and luteinizing hormone in anestrous and ovariectomized sheep.

Low levels of endogenous LHRH-like immunoreactivity (IR) were consistently detected in methanolic extracts of plasma samples from anestrous and ovariectomized sheep. Mean concentrations were similar in magnitude in the intact and castrate ewes (7.7 +/- 7.0 and 6.1 +/- 0.8 pg/ml, respectively) but revealed greater within animal fluctuations in the ovariectomized sheep (CVs: anestrous ewes = 20 +/- 3%; ovariectomized ewes = 45 +/- 10%). Patterns of plasma LHRH-like IR and LH levels were not obviously related. Differences in levels of LHRH-like IR did exist between ewes and in the ovariectomized sheep the levels were positively correlated (r = .83, P less than ,05) with the pituitary LH response to synthetic LHRH injection (0.25 micrograms). Large plasma volumes (250 ml) were extracted using chloroform, methanol and acetic acid and then chromatographed using Sephadex LH-20. Plasma LHRH-like IR could be concentrated and was found to have a column elution volume coincidence with that of synthetic LHRH. These data indicate that there is a substance in ovine plasma which is close in size, solubility and IR to sLHRH. It does not reflect LH levels in either magnitude or pattern but does exhibit a coincident increase in variation with plasma LH levels following ovariectomy and appears to be associated with the pituitary responsiveness.

Animals↗