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PubMed2000

Evidence suggesting that the potentiating action of neuropeptide Y on luteinizing hormone (LH)-releasing hormone-induced LH release remains unaltered in aged female rats.

Several lines of evidence suggest that one of the mechanisms by which the hypothalamic neuropeptide Y plays an obligatory role in the preovulatory luteinizing hormone (LH) discharge in young rats is to potentiate the action of LH-releasing hormone (LHRH) on LH release at the level of the pituitary. This study examined whether an alteration in the potentiating action of neuropeptide Y on LHRH-induced LH release may contribute to the attenuation or absence of LH surges during female reproductive ageing. Young regularly cycling (2-3-month-old) and old constant oestrous (19-20-month-old) rats ovariectomized for 7 days were primed with oestradiol-17beta-filled Silastic capsules. Two days later, rats received s.c. progesterone at 09.00 h and then were injected i.p. with either saline or pentobarbital at 13.30 hours. Pentobarbital-treated rats received i.v. pulses of neuropeptide Y, LHRH, a combination of neuropeptide Y and LHRH, or saline, every 30 min from 14.00 to 18.00 h via a jugular cannula. Hourly blood samples were collected between 11.00 and 21.00 h. In old rats, the progesterone-induced LH surge was significantly attenuated and delayed as compared to that of young rats. Pentobarbital injection completely blocked the LH surge. Neuropeptide Y pulses alone had no significant effect on LH release. In contrast, LHRH pulses increased LH release in both age groups, although the response was significantly reduced in older rats. While combined pulses of neuropeptide Y and LHRH significantly increased LH release in both young and old rats as compared to that of LHRH alone, the potentiating action of neuropeptide Y on LHRH-induced LH release remained unchanged between the two age groups. These results, together with our recent demonstration of altered hypothalamic neuropeptide Y neuronal activity in middle-aged pro-oestrous rats, suggest that a deficit in neuropeptide Y secretion and action in the hypothalamus, rather than a decrease in pituitary responsiveness to neuropeptide Y, may partially be responsible for the absence of LH surges in old rats.

Aging↗
PubMed1984

A new method for studying pituitary responsiveness in vivo using pulses of LH-RH analogue in ewes passively immunized against native LH-RH.

In two experiments with ovariectomized ewes, the plasma levels of LH and FSH were measured following passive immunization against LH-RH. The pulsatile secretion of LH was inhibited and the levels of the hormone fell quickly and were undetectable within 24 h. The levels of FSH fell more slowly and were always detectable. In the second of the experiments, pulses of LH of normal amplitude were re-established in the immunized ewes by hourly intravenous injections of 200 ng of Des-Gly10 (Pro9)-LH-RH Ethylamide, a synthetic analogue of LH-RH that does not cross-react with the antiserum yet has similar biological activity to native LH-RH. The analogue was injected over 6 h and had no detectable effect on the levels of FSH. When the ewes were injected with 50 micrograms of oestradiol benzoate, the LH responses to the analogue were completely inhibited for 4-5 h then slowly recovered to normal levels. The oestrogen injection also depressed the levels of FSH for varying amounts of time. On the basis of the normal LH patterns and responses to oestrogen, we conclude that combining passive immunization against LH-RH with injections of an LH-RH analogue provides a valuable model for testing factors that affect pituitary responsiveness to LH-RH.

Animals↗
PubMed1976

[Effects of a new analogue of LH-RH, D-Ser(TBU)6- EA10-LH-RH, on gonadotropin liberation in males (author's transl)].

Effects on the secretion of gonadotropins by D-Ser (TBU)6-EA10-LH-RH were investigated in 7 male volunteers without known endocrine disturbances. One week after subcutaneous injection of 100 mug of LH-RH the probands were given 5 mug of the LH-RH analogue subcutaneously into the abdominal wall. LH, FSH and testosterone concentrations were estimated in the serum and compared with each other at varying intervals after each injection. LH-RH caused a marked increase of the LH content in serum after 20 minutes with a maximum after 40 minutes. The effect of the analogue occurred with a delay. After 40 minutes an LH level was reached which still persisted 6 hours later. Contrary to LH there were considerable individual differences in serum FSH levels. In the initial phase after injection of LH-RH and LH-RH analogue that increase of the FSH level in serum was almost parallel. However, the analogue showed a marked depot effect. Serum concentrations of testosterone showed no significant changes after administration of the releasing hormones. D-Ser(TBU)6-EA10-LH-RH is approximately 20 times effective as LH-RH. A dose of 5 mug is effective for 6-8 hours.

Abdominal Muscles↗
PubMed1991

Comparison of a rapid, quantitative and automated assay for urinary luteinizing hormone (LH), with an LH detection test, for the prediction of ovulation.

The prediction of ovulation is necessary for oocyte aspiration in a spontaneous cycle and can be reliably achieved only by measuring luteinizing hormone (LH). Since radioimmunoassays of LH take too long for repeated measurements on the same day, we evaluated the possibility of adapting a rapid and fully automated assay of serum LH for use with urine samples. The study group comprised spontaneously ovulating women (38 cycles) who requested artificial insemination. Their serum oestradiol (E2) levels, ultrasound profile (US) and thrice daily urinary LH levels were determined from day 10 of their menstrual cycle. These patients were followed until US signs of follicular rupture were recorded. In all patients, a well-defined LH peak was measured in the urine. This peak lasted 12-15 h and was followed in 35 cycles (no US available for 3) by follicular rupture 9-51 h later. The data were grouped according to the time of the LH peak on day 0. Patients experiencing an LH peak between 0300 h and 0700 h on day 0 had significantly lower levels of E2 on day 0 compared to those with an LH peak between 2200 h and midnight. This is due to the fact that in the patients with an LH peak between 0300 h and 0700 h, E2 levels were already decreasing (from day 1 to day 0), whereas in those with the LH peak between 2200 h and midnight E2 levels were still increasing on the morning of day 0. We conclude that the 30-min IMX LH assay is a reliable, rapid and readily acceptable method for measuring urinary LH and for the prediction of ovulation.

Adult↗
PubMed1991

Correlations between mean LH levels and LH pulse characteristics: differences between normal and anovulatory women.

OBJECTIVE: Since LH secretion occurs as a series of pulses, relationships between mean LH levels and LH pulse characteristics are to be expected. The aim of this study was to determine whether such relationships are similar in normal women and anovulatory patients. DESIGN: We studied the correlations between mean LH levels and the products amplitude x frequency and area x frequency of LH pulses in normal women and in patients with disorders of ovulation. Blood samples were taken from each subject every 10 minutes during 6 hours on the 8th day after the last menses. PATIENTS: The patients were divided into three groups: patients with polycystic ovary syndrome (n = 11), patients with idiopathic anovulation (n = 14) and patients with short luteal phase (n = 13). Their results were compared to those of 12 normal women. MEASUREMENTS: LH was evaluated with an immunoradiometric assay. LH data were analysed with a 3 standard deviation threshold criterion for significant peaks, and with cluster analysis algorithm using 1, 2.5 and 5% false positive error rates and 'optimal parameters' (which give less than 5% false positive and false negative error rates in LH male data). RESULTS: Highly significant correlations between amplitude x frequency, area x frequency and mean LH were found in normals and patients with short luteal phase; no significant correlation was found in patients with polycystic ovary syndrome, while significant correlations were found in patients with idiopathic anovulation only with some of our criteria for peak detection. CONCLUSION: The differences that we found between the groups suggest that when commonly used methods are employed to determine LH pulse characteristics, most of the significant LH pulses are taken into account in normals and patients with short luteal phase, but not in anovulatory patients, especially in patients with polycystic ovary syndrome. This method using two correlations appears to be a simple and useful way to show the differences in the mechanisms by which mean LH levels are achieved in normal subjects and patients.

Adult↗
PubMed1988

LH subunit mRNA concentrations during LH surge in ovariectomized estradiol-replaced rats.

In cycling rats, pituitary concentrations of luteinizing hormone (LH) beta-subunit mRNA increase two- to threefold before the afternoon proestrus LH surge without a corresponding increase in alpha-subunit mRNA. Estradiol (E2) treatment is known to allow expression of daily LH surges in ovariectomized (OVX) rats, and the timing, magnitude, and duration of LH secretion is similar to the LH surge on proestrus. The present study was conducted to examine whether the regulation of LH subunit mRNAs during the LH surge in OVX-E2-treated rats is similar to that present on proestrus. Female Holtzman rats were OVX and Silastic implants containing E2 were inserted subcutaneously under ether anesthesia. Some animals received bromocriptine (0.6 mg sc, twice/day beginning 1 h before surgery). On the 2nd day after surgery, groups of animals (n = 4-10/group) were decapitated at intervals between 1000 and 2100. LH and prolactin (PRL) levels were measured in trunk blood. LH subunit mRNA concentrations in the pituitaries were measured by dot-blot hybridization assay. In OVX-E2 rats the LH surge occurred at 1830 and was accompanied by a selective twofold increase in alpha-subunit mRNA (from 266 +/- 18 to 459 +/- 61 pg cDNA bound/100 micrograms pituitary DNA) and maximum values were present at 1730. LH beta-subunit mRNA (m = 29 +/- 1 pg cDNA bound/100 micrograms pituitary DNA) was unchanged throughout the day. Bromocriptine treatment resulted in the suppression of serum PRL (m = 23 +/- 2 ng/ml) and the LH surge was delayed by 1-1.5 h and somewhat blunted.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Luteinizing hormone (LH)-releasing hormone: effects on maintenance of immunoreactive follicle-stimulating hormone and LH in adenohypophysial cells.

We investigated the importance of LHRH on the maintenance of FSH and LH immunoreactivity in gonadotrophs. Hypophysectomized orchidectomized hamsters (hosts) each received an allograft of a 7-week-old male hamster pituitary gland beneath their right renal capsule. Starting 6 days after transplantation, hosts were injected sc, twice daily with 1 micrograms LHRH or vehicle for 16 days. Twelve hosts in each group were killed by decapitation 16 h after the last injection. Allografts from six of the hamsters in each group and pituitary glands in situ from 10-week-old normal males were prepared for histological examination. Sections of tissue were stained for FSH or LH and with hematoxylin. Allografts from the remaining hamsters were homogenized to measure FSH and LH concentrations. In allografts from the vehicle-treated hosts, 22.8% of adenohypophysial cells stained for LH, while only 16.9% stained for FSH. In allografts from LHRH-treated hosts, 22.6% and 23.8% of the adenohypophyses cells stained for LH and FSH, respectively. Adenohypophyses that developed for the same length of time in situ had 24.8% and 24.1% of the cells staining for LH and FSH, respectively. Matching of some of the FSH and LH cells in serial flip-flopped sections of tissue from all hamsters revealed that many if not all gonadotrophs contained LH. LH- and FSH-containing cells in allografts were similar in size and shape, but were smaller and more circular in profile than those observed in situ. Treatment of hosts with LHRH did not alter gonadotroph size or shape, but it did reduce allograft LH concentration and elevate the serum FSH concentration compared to that in the vehicle-treated hamsters. These results suggest that in the hamster LHRH 1) plays a major role in maintaining FSH immunoreactivity in adenohypophysial tissue, 2) does not play a role in maintaining numbers of immunoreactive LH cells in adult adenohypophysial tissue, and 3) functions to maintain FSH synthesis at least in part in cells that contain LH.

Animals↗
PubMed1982

Histochemical study of the rat anterior pituitary LH-gonadotroph after administration of luteinizing hormone releasing hormone (LH-RH).

The aim of this study was to identify the LH-gonadotroph, aided by histochemical demonstrations of adenylate cyclase and acid phosphatase activities in 60-day-old male rats, after a single 100 micrograms injection of luteinizing hormone-releasing hormone (LH-RH). The results obtained are as follows: 1) Separation of the lysosomes from the large secretion granules in the LH-gonadotroph was accomplished in order to demonstrate acid phosphatase, the marker enzyme of lysosomes. 2) The large granules in the LH-gonadotroph decreased remarkably in number within 5 min after LH-RH injection. 3) A marked and prolonged increase in adenylate cyclase activity was observed on the plasma membrane of the LH-gonadotroph after LH-RH injection; this increase continued up to 30 min. 4) At 60 min after LH-RH injection the small secretion granules began to decrease in number. 5) Losing the large granules due to the LH-RH treatment, the LH-gonadotroph resembled the FSH-gonadotroph. From these observations it appears that the FSH-gonadotroph is an immature or storage state LH-gonadotroph and that it changes from an LH-gonadotroph into an FSH-gonadotroph on the loss of its large secretion granules.

Acid Phosphatase↗
PubMedDate not supplied

The predictive value of five different urinary LH kits in detecting the LH surge in regularly menstruating women.

OBJECTIVES: To compare the predictive value of five different urinary LH kits at detecting the LH surge in regularly menstruating, reproductive-age women. DESIGN: Single center, prospective study. SETTING: University of Tennessee, Obstetrics and Gynecology department. INTERVENTION: Eleven regularly menstruating women collected urine daily from cycle days 10 through 18. Urinary LH was quantitated by radioimmunoassay. Transvaginal sonography was performed to document ovulation. Three different lots of Clear Plan Easy, OvuKit, OvuQuick, Sure Step, and EZ LH were evaluated. MAIN OUTCOME MEASURE: Correlation of urinary LH test kit results with urine LH value determined by RIA. RESULTS: Peak urinary LH values by RIA ranged from 13.5 mIU/mL to 73.0 mIU/mL. The lowest level detected as positive by LH kits ranged from 25.5 mIU/mL to 48.7 mIU/mL. Lot-to-lot variations were rare. Follicular collapse occurred within 24 hours of the urinary LH peak in 8 of 10 (80%) and by 48 hours in the remaining 2 subjects. CONCLUSIONS: The percentage of LH surges detected by urinary LH kits ranged from 50% to 100%. The lowest LH value detected as positive varied almost twofold between different kits. Manufacturers should indicate the detection limit of their kits in mIU/mL.

Adult↗
PubMed1997

[An image analysis of the morphological changes of LH cells during LH release peak induced by LHRH in male rats].

The relationship between the peak of LH release induced by exogenous LHRH and morphological change of LH cells in male rats was investigated by ABC Affinity histochemistry and qualitatively characterized by Medical Image Processing System-I. The serum LH concentration was determined by RIA. During the period of basal secretion of LH (3.76 +/- 0.39 ng/ml), the LH cells might be assigned at a storage state. Most of such cells (56.7%) are round and large, and their cross sectional areas are larger then 340 micron 2, usually containing large vacuoles, while the smaller cells of X-sectional area less then 190 micron 2 counted only 2% of the total population. Thirty minutes after injection of LHRH the serum LH level increased significantly (6.46 +/- 1.6 ng/ml, P < 0.01), there appeared a lot of small angular cells, the average cross sectional areas of LH cells decreased significantly (P < 0.0001). When LHRH was injected at sixty minutes, the LH level reached a peak (18.78 +/- 0.79 ng/ml), the number of the large cells decreased to only 4%, while the small cells increased to 66%, vacuoles were almost disapperanced and a large part of cells (52.6%) became irregular. Thereafter, the LH serum gradually subsided to its original basal level with attendant resumption of the morphology of the LH cells at storage state. It appears that the morphological changes, such as size, shape, vacuoles and so on, of the LH cells may serve as an important index for showing the effect of LHRH on LH secretion.

Animals↗
PubMed1985

Naloxone increases bioactive LH in man: evidence for selective release of early LH pool.

Opioid peptides inhibit LH secretion and the opiate antagonist naloxone provokes increases in plasma LH levels by release of endogenous GnRH from the hypothalamus. To explore the effect of endogenously released GnRH on the mobilization of bioactive LH pools, the bioactive LH response to a single iv bolus dose of 20 mg naloxone has been evaluated and compared to the immunoactive pattern of the hormone in eight young normal male volunteers. Blood samples were withdrawn at 15, 30, 45, 60, 90, 120 min after naloxone injection and LH levels were measured by RIA and rat interstitial cell testosterone (RICT) bioassay. A significant increase in both bio and immuno active LH was observed in all subjects after 15-30 min (p less than 0.05 to p less than 0.001), reaching maximal levels at 30-60 min for both forms of the hormone. The time course of the bioactive LH response magnified the immunoactive LH pattern, and the maximum fold increases were 1.4 and 1.3 fold (62.4 +/- 5.5 SE and 25.0 +/- 3.7 SE mIU/ml) from basal bio and immuno LH levels of 25.9 +/- 4.3 SE and 11.1 +/- 2.0 SE mIU/ml respectively. An early single peak response of bio and immunoactive LH was observed in six subjects while a biphasic pattern was observed in two subjects with a clearly defined and prominent early pool followed by a second pool of higher magnitude. Both bio and immunoactive LH levels began to decline at 45-60 min, but in most subjects remained significantly elevated by about 30% above the basal values at 120 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Interleukin-1 beta inhibits the endogenous expression of the early gene c-fos located within the nucleus of LH-RH neurons and interferes with hypothalamic LH-RH release during proestrus in the rat.

The ability of central interleukin-1 beta (IL-1 beta) administration to modulate the hypothalamic LH-RH release as well as the endogenous expression of the c-fos protein located within the nucleus of LH-RH neurons was examined during the afternoon of proestrus in rats. In a first series of experiments, 50 or 100 ng IL-1 beta were infused into the lateral ventricle of the rat brain at either 08.30, 12.00, 14.30, or 17.00 h of proestrus. The animals were then perfused transcardially with a solution of 4% paraformaldehyde from 17.30 and 18.00 h. In a second series of experiments, the rats were equipped with an intracerebroventricular (i.c.v.) cannula in the lateral ventricle and a push-pull cannula into the median eminence (ME), and LH-RH secretion was measured during the afternoon of proestrus. The third experiment investigated the putative role of corticotropin-releasing factor (CRF) in modulating the inhibitory effect of IL-1 beta on LH secretion by infusing CRF antagonists before the i.c.v. administration of the cytokine to gonadectomized male and female rats. The central infusion of 50 or 100 ng IL-1 beta at 12.00 h completely blocked the spontaneous expression of c-fos protein which normally occurs in the nucleus of LH-RH neurons between 17.30 and 18.00 h on proestrus. In contrast, 50 ng IL-1 beta was less effective (P < 0.05) when administered at 08.30 h, and totally without effect when infused at 14.30 h. Infusion of 50 ng IL-1 beta also markedly suppressed the hypothalamic release of LH-RH in proestrus rats bearing a push-pull cannula into the ME, and significantly decreased plasma LH levels in both gonadectomized male and female rats. Finally, we observed that the central administration of CRF antagonists did not modify the inhibitory effects of the cytokine on the activity of the hypothalamic-pituitary-gonadal (HPG) axis. These results provide the first direct evidence that IL-1 beta is a potent inhibitor of LH-RH neuronal activity during the proestrus LH surge in intact cycling rats. As central administration of this cytokine completely inhibited the endogenous expression of c-fos protein within the nucleus of LH-RH neurons, our findings also suggest that IL-1 beta acts at the level of LH-RH perikarya.

Animals↗
PubMedDate not supplied

Effects of in vivo pretreatment with D-Trp-6-LH-RH on prolactin and LH secretion by pituitary glands in vitro.

In order to study a possible direct action of LH-RH analogs on the pituitary lactotrophs, we investigated the effect of long-term in vivo pretreatment with D-Trp-6-LH-RH on in vitro secretion of PRL and luteinizing hormone (LH) by the pituitary glands from male and female rats. In vivo pretreatment with D-Trp-6-LH-RH (50 micrograms/day, SC) for 15 days greatly reduced basal in vitro PRL release (p less than 0.01) in female, but not in male pituitary glands. TRH-stimulated PRL secretion was not affected by pretreatment with D-Trp-6-LH-RH in female rats, but was impaired in male pituitaries. Acute in vitro exposure to D-Trp-6-LH-RH did not modify PRL secretion by female pituitary glands pretreated in vivo with the analog. However, this same in vivo pretreatment greatly decreased PRL release from male pituitaries (p less than 0.01). Basal in vitro LH release by male pituitary glands was partially lowered by in vivo pretreatment with D-Trp-6-LH-RH, as compared to controls (p less than 0.01), while basal LH release in female pituitaries remained at control levels. Finally, D-Trp-6-LH-RH-induced stimulation of in vitro LH release was severely impaired in female pituitaries (p less than 0.01) but only slightly reduced in the males.

Animals↗
PubMed1982

Treatment of hypogonadotropic hypogonadal male patients with the luteinizing hormone-relasing hormone (LH-RH) anolog D-Ser(TBU)6 EA10 LH-RH: transient disappearance of gonadotropin stimulation.

We have studied the effect of prolonged treatment with a long-acting luteinizing hormone-releasing hormone (LH-RH) analog (D-Ser-(TBU)6 EA10 LH-RH in six patients with isolated gonadotropin deficiency. Before treatment, all subjects responded to LH-RH (100 microgram intravenously [IV]); one responded immediately, and five after 5 daily infusions of LH-RH (200 microgram). Treatment by LH-RH analog (348 microgram every 2 days with a nasal spray for 90 or 120 days) is only efficient for 1 month; a consistent increase in serum LH and a slight increase in testosterone (T) were observed in all patients, but no increase of serum follicle-stimulating hormone (FSH) was detectable. Then a paradoxical effect appeared: LH and T levels returned to the basal values. Moreover, this treatment induced refractoriness of the pituitary to LH-RH for several months after the end of treatment. The appearance of antibodies to LH-RH and LH-RH analog was eliminated. A pituitary response was obtained in three patients when a new LH-RH stimulation was repeated 7 and 11 months after the end of treatment. The mechanism of this pituitary desensitization is discussed.

Adolescent↗
PubMed2002

Differential requirement for pulsatile LH during the follicular phase and exposure to the preovulatory LH surge for oocyte fertilization and embryo development in cattle.

The requirement for pulsatile LH and the LH surge for the acquisition of oocyte fertilizing potential and embryo developmental competency was examined in Zebu heifers. Follicular growth was superstimulated using the GnRH agonist-LH protocol in which pulsatile LH and the preovulatory LH surge are blocked. In experiment 1, heifers were assigned on Day 7 of the estrous cycle to receive: group 1A (n = 5), 1.5 mg norgestomet (NOR) implant; group 1B (n = 5), GnRH agonist implant. Follicular growth was superstimulated with 2x daily injections of FSH from Day 10 (a.m.) to Day 13 (p.m.), with PGF2alpha injection on Day 12 (a.m.). Heifers were ovariectomized on Day 15 (a.m.) and oocytes were placed immediately into fertilization, without 24 h maturation. Respective cleavage and blastocyst development rates were: group 1A, 0/64 oocytes (0%) and 0/64 (0%); group 1B, 34/70 oocytes (48.6%) and 2/70 (2.9%). In experiment 2, heifers were assigned on Day 7 of the estrous cycle to receive: group 2A (n = 10), 1.5 mg NOR implant; group 2B (n = 10), GnRH agonist implant; group 2C (n = 10), GnRH agonist implant. Follicular growth was superstimulated as in experiment 1 above. Heifers in groups 2A and 2B received an injection of 25 mg LH on Day 14 (p.m.) and all heifers were ovariectomized on Day 15 (a.m.); oocytes were placed immediately into fertilization without 24 h maturation. Cleavage rates were similar for heifers in group 2A (84/175 oocytes, 48.0%), group 2B (61/112 oocytes, 54.5%) and group 2C (69/163, 42.3%). Blastocyst development rates were similar for heifers in group 2A (22/175 oocytes, 12.6%) and group 2B (25/112 oocytes, 22.3%) and lower (P < 0.05) for heifers in group 2C (9/163 oocytes, 5.5%). Oocytes obtained from heifers treated with GnRH agonist, without injection of exogenous LH, underwent cleavage indicating that neither pulsatile LH nor the preovulatory LH surge are obligatory for nuclear maturation in cattle oocytes. Exposure to a surge-like increase in plasma LH increased embryo developmental competency indicating that the preovulatory LH surge promotes cytoplasmic maturation. The findings have important implications for controlling the in vivo maturation of oocytes before in vitro procedures including nuclear transfer.

Animals↗
PubMed2003

Suppression and recovery of LH secretion by a potent and selective GnRH-receptor antagonist peptide in healthy early follicular-phase women are mediated via selective control of LH secretory burst mass.

AIM: GnRH antagonists are competitive inhibitors of GnRH receptors. Their administration induces prompt suppression of the gonadal axis. In animals, GnRH antagonists upregulate the activity of GnRH-secreting neurones, which could cause gonadotrophin rebound following inhibition. The aim of this study was to evaluate the effects of a potent GnRH antagonist, Teverelix (TEV), on the gonadal axis in healthy young women. SUBJECTS AND MEASUREMENTS: In nine women [20-35 years old, body mass index (BMI) 19-25 kg/m2] in the early follicular phase, serum LH and FSH levels were evaluated every 10 min from 08.00 to 12.00 h before, and 24 h and 96 h after TEV injection (2.5 mg in 1 ml subcutaneously on day 0). Serum gonadotrophin and oestradiol levels were also evaluated at baseline and at 6, 8, 12, 48, 72 h after TEV. RESULTS: The antagonist reduced both serum LH and FSH concentrations; LH levels were significantly and promptly reduced at +6 h (nadir at +8 h) until +48 h and recovered at +72 h, while FSH levels were reduced (P<0.05) 24 h after the antagonist and normalized at +48 h. LH (but not FSH) concentrations at +96 h exceeded baseline (P<0.05). TEV suppressed oestradiol concentrations (P<0.05) with a nadir at +24 h, comparable reduction at +48 h and recovery to baseline at +72 h. Deconvolution analysis showed that the antagonist peptide suppressed (P<0.02) the pulsatile production rate, burst mass and amplitude of LH on day 1. Pulsatile FSH secretion also fell at this time (P<0.05). LH and FSH pulse frequency were not modified by TEV. At +96 h, LH pulsatility did not significantly differ from that at baseline. Suppression of mean LH or FSH concentrations did not affect the relative pattern regularity (approximate entropy) of LH and FSH secretion. CONCLUSIONS: This study demonstrates that the acute administration of a potent GnRH antagonist induces prompt inhibition of the gonadal axis lasting for 2 days in women due to mechanistically specific suppression of LH secretory burst mass and the mean FSH secretion rate. The trend toward rebound release of LH following the end of the pharmacological effect of the antagonist could reflect a rise in endogenous GnRH activity.

Adult↗
PubMed1975

Stimulation of LH release and ovulation in the rat by cutaneous application of luteinizing hormone-releasing hormone (LH-RH) in dimethyl sulfoxide (DMSO).

The efficacy of cutaneously applied luteinizing hormone releasing hormone (LH-RH) in stimulating LH release in the chronically ovariectomized, estrogen/progesterone-blocked rat and ovulation in the chlorpromazine-blocked, proestrous rat was investigated. Following the cutaneous application of 25 or 100 mug of LH-RH in 100% dimethyl sulfoxide (DMSO), serum LH rose to a peak at 1 hr, then declined toward basal levels in the ensuing 3 to 4 hr. LH-RH applied cutaneously in either 100% DMSO or 0.9% NaCl was also capable of inducing ovulation in the chlorpromazine-blocked, proestrous rat; however, LH-RH in 0.9% NaCl did not yield a linear log-dose-response relationship, therefore a valid ED50 potency ratio for DMSO/0.9% NaCl could not be estimated. Nonetheless, 0.9% NaCl was a considerably less effective cutaneous vehicle than DMSO. Cutaneous application of LH-RH in DMSO in doses of 100, 50, 25, 10, 5, 2.5 and 1 mug induced ovulation in 100%, 100%, 90%, 73%, 30%, 10% and 0% of the rats, respectively. When the percent ovulation response was transformed to probits and plotted against the logarithm of the LH-RH dose an approximately linear log dose-response was obtained; the same relationship also held true for ovulation induction following sc LH-RH administration. In turn, the ED50's of these two parallel dose-response curves yielded a potency ratio estimate (sc/cutaneous) of 0.025, suggesting that 2.5% of the cutaneously applied LH-RH dose was absorbed through the skin in a biologically active form. These data indicate that DMSO privdes a convenient cutaneous vehicle for the administration of LH-RH.

Administration, Topical↗
PubMed1990

The role of LH in the autofeedback inhibition of LH and FSH secretion in ovariectomized rats.

This study examined the role of exogenous LH in the autofeedback regulation of LH and FSH release in ovariectomized rats. The rats were implanted with third ventricular cannulae three weeks after ovariectomy and fitted with silastic jugular cannulae one week later. Baseline hormone levels were established on the day of experimentation in conscious, unrestrained animals. Thereafter, experimental animals received intraventricularly (IVT) either a 9 ug or 20 ug dose of a purified preparation of human (h)LH that did not crossreact in our rLH RIA. In response to 20 ug, but not 9 ug of LH, plasma levels of both LH and FSH were significantly reduced during the following one hour period compared to values in controls receiving buffer IVT. Administration of ovine (o)LH (6 ug, IVT), a preparation which crossreacts in the rLH RIA, significantly elevated plasma levels of detectable LH during the experimental period indicating that LH reaches the blood stream from the third ventricle and, thus, may effect endogenous hormone release at either the pituitary or hypothalamic levels. However, in animals preinjected with 9 or 20 ug of hLH IVT one hour earlier the surge of both LH and FSH in response to LHRH (25 ng iv) was not different from that in the buffer-injected controls receiving LHRH which indicates that pituitary responsiveness was not suppressed by the effective dose of hLH. The results of this study suggest that the inhibitory shortloop feedback of LH on endogenous LH and FSH secretion in ovariectomized rats occurs at the level of the hypothalamus.

Animals↗