Synthetic Luteinizing Hormone Releasing Factor Research Articles

Hormone Ontogeny in the Ovine Fetus: XIX: The Effect of a Potent Luteinizing Hormone-Releasing Factor Agonist on Gonadotropin and Testosterone Release in the Fetus and Neonate'

To investigate further the role of the hypothalamic luteinizing hormone releasing factor (LRF) pulse generator and the pituitary LRF receptor in the regulation of gonadotropin secretion and gonadal steroidogenesis in the ovine (O) fetus and neonatal lamb, we measured the increment (the difference between the concentration of plasma LH at time 0 and peak LH) in oLH (delta oLH) and oFSH (delta oFSH) responses to a potent LRF agonist, D-Trp6Pro9NEt-LRF (LRF-A), after consecutive daily doses in 17 ovine fetuses (six females, 11 males) and in 15 neonatal lambs (six females, nine males). Seven of the lambs had been studied as fetuses. In addition, plasma concentrations of testosterone (T) and androstenedione (delta 4A) were measured in nine male fetuses. After a stimulatory response to the first dose of LRF-A, the mean delta oLH and delta oFSH responses in the 106- to 118-d gestation fetuses of both sexes were significantly suppressed by the fourth dose and in the neonatal lamb by the second dose. Suppression was sustained throughout the duration of LRF-A therapy which included the gestational interval when the fetal pituitary exhibits its greatest responsiveness to an acute dose of synthetic LRF. The duration of oLH and oFSH suppression after cessation of LRF-A therapy was studied by measuring the delta oLH and delta oFSH responses to LRF before and at intervals after LRF-A therapy. In the fetus, the delta oLH and delta oFSH responses remained significantly decreased 7-8 d after the agonist was discontinued.(ABSTRACT TRUNCATED AT 250 WORDS)

Luteinizing hormone-releasing factor increases release of human chorionic gonadotrophin in isolated cell columns of normal and malignant trophoblasts.

The effect of synthetic luteinizing hormone-releasing factor (LRF) on release of human chorionic gonadotrophin (hCG) was studied by isolated cell columns of normal syncytiotrophoblasts and choriocarcinoma (BeWo) cells. After LRF stimulation the release of hCG by the normal trophoblasts increased up to 4-fold and release by the malignant trophoblasts increased up to 6-fold, indicating a specific effect of LRF on normal and malignant trophoblast cells.

Induction of ovulation and pregnancy with pulsatile luteinizing hormone releasing factor: dosage and mode of delivery

The efficacy of intravenous and subcutaneous routes for pulsatile delivery of differing dosages of synthetic luteinizing hormone releasing factor (LRF) for ovulation induction were evaluated sequentially in two patients with presumed deficiency of endogenous LRF: isolated gonadotropin deficiency and pituitary stalk transection with hyperprolactinemia. Observations were made of the amplitude and duration of the induced LH-FSH pulses, of follicular growth and ovulation (via ultrasound), and of ovarian steroids. Remarkable differences in each of these parameters were found between the two modes of LRF delivery. LRF pulses administered subcutaneously resulted in inappropriate gonadotropin secretion, arrest of follicular development, elevated ratios of E1/E2 and androgens/estrogens, and the appearance of acne - features of polycystic ovary syndrome. In contrast, the first intravenous course of pulsatile LRF induced orderly follicular maturation and ovulation with subsequent pregnancy in both subjects. From these findings we conclude that, in these patients, the intravenous mode of delivery of LRF pulses was superior to the subcutaneous route at all doses tested.

Characterization of placental luteinizing hormone-releasing factor-like material.

High pressure liquid chromatography (HPLC) and radioimmunoassay were employed to characterize luteinizing hormone-releasing factor (LRF)-like material in the human placenta. Methanol extracts of the placenta were washed with acetic acid and chloroform, further purified on coarse octadecylsilane columns, fractionated on HPLC, and tested by radioimmunoassay. In HPLC, placental LRF had the same retention time as synthetic LRF, and such fractions gave an inhibition curve which was parallel to that of synthetic LRF in radioimmunoassay. It is concluded that human placental LRF is similar or identical to LRF in the central nervous system.

Immunohistochemical demonstration of luteinizing hormone-releasing factor-like material in human syncytiotrophoblast and trophoblastic tumours.

Luteinizing hormone-releasing factor (LRF)-like immunoreactivity was demonstrated by a three layer bridge immunoperoxidase technique in the syncytiotrophoblast of early human placenta, hydatidiform mole and choriocarcinoma. Anti-LRF antiserum was prepared by immunizing rabbits with synthetic LRF coupled to bovine serum albumin (BSA). The immunoreactive site of LRF reacting with the antiserum resided between residues Tyr(5) and Gly(10)-NH2. Syncytiotrophoblast cells of the normal placenta from the first half of pregnancy and trophoblastic tumours, showed staining with anti-LRF antiserum after solid phase immuno-adsorption with Sepharose-coupled BSA. Adjacent control sections showed no staining when prepared with anti-LRF antiserum after immunoadsorption with a Sepharose-coupled LRF-BSA conjugate. The findings of LRF-like material in the placenta prompted us to examine the effect of exogenous LRF on the circulating levels of placental proteins and protein hormones synthesized by the syncytiotrophoblast. Serum levels of chorionic gonadotrophin, pregnancy-specific beta-l-glycoprotein, placental protein five, and placental lactogen remain unaltered for 2 h after an intravenous bolus of LRF (100-300 micrograms) to ten pregnant volunteers admitted for legal abortion between 8 and 18 weeks of gestation. The significance of LRF-like material for the endocrinology of the normal and malignant trophoblast remains to be elucidated.

Direct Feedback Inhibition by Endogenous Testosterone on the Pituitary in Man

Synthetic luteinizing hormone-releasing factor (LRF) was injected iv to 2 healthy menat successive 1-week intervals with increasing amounts of LRF from 50 to 800 μg and the effects on LH and testosterone titers just before and after successive stimulations were studied. The weekly baseline levels of plasma LH progressively decreased seven days after administrationof increasing amounts of injected LRF. Baseline LH titers fell to the lower portion of the normal range (48 ng/ml) in one man and to under the normal range (29 ng/ml) in the other. Higher peak values of plasma LH (up to 507 and 932 ng/ml) response to LRF occurred within 1 h with increased injected LRF from 50 to 100 or 200 μg. With larger doses of LRF, the peak values of plasma LH were much lower, as low as 185 and 277 ng/ml. These titers were close to the basal normal range. Weekly baseline titers of testosterone increased markedly following increased LRF. Peak plasma testosterone levels occurred within 180 min of each LRF stimulation. Testoster...

Endocrine Function of Pituitary-Ovarian Axis in Anovulation

Forty-one anovulatory patients consisting of twenty with primary amenorrhea and twenty-one with secondary amenorrhea were investigated by ovarian biopsy and endocrine studies. The ovaries of these patients could be divided into two groups, one with ovarian follicles and the other without ovarian follicles. The ovaries with ovarian follicles could be further divided on the basis of the presence or absence of tertiary follicles; groups with tertiary follicles (high developmental stage) and without tertiary follicles (low developmental stage).The serial measurements of serum gonadotropins and urinary total estrogens were performed in all anovulatory patients. The pituitary responsiveness to synthetic luteinizing hormone releasing factor (LRF) and the ovarian responsiveness to gonadotropins [human menopausal gonadotropin (HMG) and human chorionic gonadotropin (HCG)] in patients with primary and secondary amenorrhea were tested and compared with those in normal control subjects in the follicular phase. Histological and histochemical examination of the ovaries showed some significant differences between the ovaries of the patients with primary amenorrhea and those with secondary amenorrhea.Of 20 patients with primary amenorrhea, 10 had no ovarian follicles. By contrast, of 21 patients with secondary amenorrhea, 16 had highly developed follicles. More abundant steroidogenic foci were observed in most ovaries of the patients with secondary amenorrhea. The serum levels of follicle stimulating hormone (FSH) were closely related with the presence or absence of ovarian follicles as Goldenberg et al. (1973) had reported previously.Both primary amenorrheic patients without ovarian follicles and secondary amenorrheic patients with low developed follicles showed endocrinologic pictures of hypergonadotropic hypogonadism. Serum luteinizing hormone (LH) and FSH responses to LRF in these patients were markedly greater than those in normal subjects of the follicular phase. The patients with secondary amenorrhea could be divided into two groups; one with low developed ovarian follicles and the other with highly developed follicles, according to FSH responsiveness to LRF.The ovarian volume and the developmental stage of follicle growth were closely correlated with the urinary excretion of total estrogens and the ovarian responsiveness tc gonadotropin stimulation. The ovarian response to gonadotropin in patients with secondary amenorrhea was usually greater than that seen in patients with primary amenorrhea. Then, it seemed that the etiologic lesion of most patients with primary amenorrhea existed in the ovary and that of most patients with secondary amenorrhea in the hypothalamus.In most patients with highly developed ovarian follicles, induction of ovulation was successfully achieved by HMG-HCG treatment, the total amount of HMG being less than 1500 I.U.. Ovulation could be induced in 33.3% of patients with primary amenorrhea and in 61.5% of patients with secondary amenorrhea. The therapeutic results were in accord with histological findings of the ovary and the responsiveness to gonadotropin stimulation.

Correlation between integrated LH and FSH levels and the response to luteinizing hormone relasing factor (LRF).

Integrated blood plasma levels of LH and FSH and their response to the iv administration of 100 mug synthetic LRF were studied in 29 normal subjects, 12 women with Stein-Leventhal syndrome, 8 subjects with primary gonadal failure, 7 women with Sheehan's syndrome, 20 subjects with pituitary tumors, 10 subjects with idiopathic gonadotropin deficiency and 5 subjects with hypothalamic tumors. Within each group there was considerable variation in the response of LH and FSH levels to LRF. In each group there was a statistically significant positive correlation between basal integrated gonadotropin levels and the response of the levels to LRF. Both within groups and between groups, the best indicator of the response to LRF was the basal levels of FSH and LH. In subjects with hypogonadotropic hypogonadism there was no significant difference in mean basal LH levels and mean response to LRF between patients with primarily pituitary disease (pituitary tumors or Sheehan's syndrome) and conditions which might represent hypothalamic disease (hypothalamic tumors or idiopathic gonadotropin deficiency). The response to an acute, single, injection of LRF appears to more directly reflect basal gonadotropin levels rather than disease category.

Immunoreactive LRF neurosecretory pathways in mammals.

Using antisera to synthetic luteinizing hormone-releasing factor (LRF) and antisera labeled with fluorescein isothiocyanate or peroxidase, it was possible in various physiological and experimental conditions to determine the topography of the LRF secretory cells in the guinea pig. The axons of these cells form a preoptico-infundibular LRF pathway, which controls the prehypophyseal gonadotropic secretion, and various "extrahypophyseal pathways". These latter suggest that LRF, in addition to its prehypophysiotropic action, may have a neuromodulator function.

The Role of Estrogen in the Modulation of Pituitary Sensitivity to LRF (Luteinizing Hormone-Releasing Factor) in Men1

The role of estradiol in modulating pituitary gonadotropin release in the human male was studied by evaluating the effects of clomiphene on the pituitary gonadotropin response to synthetic LRF (150 mug) in 6 eugonadal men. Administration of clomiphene (100 mg single daily dose time 5 days) induced a significant elevation of the basal levels of LH, FSH, estradiol and testosterone. However, the pituitary release of LH and FSH in response to LRF was markedly diminished by the clomiphene treatment. This finding suggests that in men, as in women, endogenous estradiol provides feedback regulation of gonadotropin output by the pituitary.

THE RESPONSIVENESS OF THE ANTERIOR PITUITARY GLAND TO LUTEINIZING HORMONE RELEASING FACTOR IN RATS EXPOSED TO CONSTANT LIGHT

The responsiveness of the anterior pituitary gland to synthetic luteinizing hormone releasing factor (LH-RF) was tested in rats exposed to constant light. At a dosage of 50 ng LH-RF/100 g body wt the mean maximal increments in plasma LH and FSH were similar to those at 10.00 h of pro-oestrus. The increments in the plasma gonadotrophins at dosages of 500 and 1000 ng LH-RF/100 g body wt did not differ significantly from those at 250 ng LH-RF/100 g body wt. These findings suggest that, in contrast to rats which exhibit regular oestrous cycles, the preovulatory (post-coital) release of LH in rats exposed to constant light may depend almost entirely on the release of a relatively large amount of LH-RF into hypophysial portal vessel blood. Whereas in pro-oestrous animals a relatively small fraction of the readily releasable pool of LH is released during the spontaneous preovulatory surge, in rats exposed to constant light most releasable LH appears to be discharged during the reflex preovulatory surge of this hormone. The concentrations of radioimmunoassayable FSH in blood samples withdrawn before the injection of LH-RF support the view that FSH secretion in the rat is increased by constant exposure to light.

Daily variations of FSH, LH and testosterone response to intravenous luteinizing hormone-releasing factor (LRF) in normal men.

The responses of FSH, LH and testosterone to acute stimulation with synthetic LRF were studied in 6 healthy, fertile men aged 33.4 plus or minus 1.6 yr (X plus or minus SE). Fifty mug of LRF were given, iv at 0600 h, 1200 h, 1800 h and 0000 h, at 1-week intervals, to all 6 volunteers simultaneously. Blood samples were collected by venipuncture before (-5 and 0 min) and 8, 16, 32, 64 and 128 min after LRF injection. Plasma levels of FSH, LH and testosterone were determined by double antibody radioimmunoassay techniques. The responses of FSH and LH to LRF injection showed a clear difference at the times studied. Maximal values were obtained at 0600 h and 1800 h while the response at noon was not significant for LH and absent for FSH. Testosterone secretion showed a clear-cut response to LRF in all the subjects. At three of the four studied times (0600 h, 1800 h, 000 h) plasma testosterone was already increased at 8 min reaching its maximum at 16 min and persisted high until the end of the study. The noon response reached its maximum at the end of the test period. The daily variations of FSH and LH responses to acute LRF stimulation should be taken into consideration in clinical practive and the increment in testosterone secretion makes this test a useful indicator for androgenic testicular reserve.

Responsivity of Pituitary Gonadotropes to Luteinizing Hormone-releasing Factor in Idiopathic Precocious Puberty, Precocious Thelarche, Precocious Adrenarche, and in Patients Treated with Medroxyprogesterone Acetate

Extract: One hundred micrograms synthetic luteinizing hormone-releasing factor (LRF) were administered to 13 girls and 2 boys with idiopathic precocious puberty, 3 girls with precocious thelarche, 2 girls with precocious adrenarche, and 5 children treated with medroxyprogesterone acetate (MPA). Luteinizing hormone (LH), follicle-stimulating hormone (FSH), and sex steroid responses were assessed. The mean readily releasable LH rose to a peak of 8.4 ± 1.8 ng/ml (LER 960) in the children with idiopathic precocious puberty and was significantly greater than in normal prepubertal (1.8 ± 0.14) or pubertal children (4.9 ± 0.34). The peak plasma FSH response (8.4 ± 1.4 ng/ml) (LER 869) was higher in precocious puberty but not significantly greater than in normal prepubertal (5.3 ± 1.9) or pubertal girls (6.0 ± 1.2). The mean concentration of plasma estradiol rose significantly above resting levels after LRF in the girls with idiopathic precocious puberty. The LH response in girls with precocious thelarche and adrenarche was in the prepubertal range. In 4 of 5 children with sexual precocity treated with MPA, the LH release evoked by LRF was diminished. Speculation: Premature neural activation of hypothalamic LRF synthesis and release may occur in children with idiopathic precocious puberty. This leads to increased pituitary gonadotropin synthesis, storage, and more readily releasable LH. The higher FSH release after LRF in normal girls than boys may be a factor in the strikingly higher prevalence of idiopathic precocious puberty in girls than in boys.

Direct evidence of estrogen modulation of pituitary sensitivity to luteinizing hormone-releasing factor during the menstrual cycle.

To delineate the role of estradiol in the augmented pituitary gonadotropin responsiveness to synthetic luteinizing hormone releasing factor (LRF) seen during high-estrogen phases of the ovulatory cycles (late follicular and midluteal phases), the anti-estrogenic effect of clomiphene citrate (Clomid) on pituitary response to LRF was evaluated during different phases of the ovulatory cycle. Clomid administration (100 mg/day times 5 days) completely negates the augmented gonadotropin responses to LRF (150 mug) during late follicular and midluteal phases observed during the control studies. Thus, a quantitatively and qualitatively similar pituitary sensitivity to LRF during three distinct phases of the menstrual cycle was induced by Clomid treatment that resembles the LRF responsiveness of themale pituitary. The present study demonstrates the pituitary component of the estrogen-induced changes in the sensitivity to LRF. From this and previous data, we conclude that the increases of estradiol secretion associated with the follicular maturation and corpus luteum formation represent a major component of the feedback signal in the modulation of cyclic gonadotropin release occasioned in a large measure by the augmented pituitary sensitivity to LRF.

Immunofluorescence study of the preoptico-infundibular LRF neurosecretory pathway in the normal, gastrated or testosterone-treated male guinea pig.

Luteinizing hormone-releasing factor (LRF) has been localized in a preopticoinfundibular pathway in normal, castrated and testosterone-treated male guinea pigs, by an immunofluorescence technique. Some animals of each group were injected into the lateral ventricle with10% to 50% methanol, with or without melatonin, prior to study. Controls for the specificity of the antisera to LRF were carried out by immunohemolysis, radioimmunoassays, or blocking experiments on tissue sections, using synthetic LRF, vasopressin, oxytocin, TRF, or a lipid-free brain extract. Immunoreactive cell bodies were counted in 100 serial 10 µ sagittal sections, between two symmetric paramedian planes 1 mm apart. A maximum of 5 to 15 positive cells⁄100 sections were found in all the animals, except the castrates treated with methanol in which as many as 20 times more reactivecells were found; melatonin did not produce a further increase in number, but it did produce an increase in the intensity of the immunoreactivity of the perikarya and their processes. The perikarya of cells containing LRF were localized in 3 groups: the main group was found in the pre- and suprachiasmatic region; smaller groups were located in front of the anterior commissure and the parolfactory region. Beaded axonal pathways containing LRF traveled from the perikarya of the two first groups through the hypothalamus, in a caudal direction to end in the infundibulum around portal capillaries. Along their course these axons appeared to branch and at times to make synaptic contacts with cell bodies. In addition to the“preoptico-infundibular pathway”, some extrahypophyseal LRF pathways have been observed, some of which suggested a role for LRF in the control of sexual behavior. (Endocrinology95: 1416, 1974)

Gonadotrophin secretion after electrical stimulation of the preoptic area during the oestrous cycle of the rat.

SUMMARY The responsiveness of the hypothalamo-hypophysial axis to electrical stimulation of the medial preoptic area was tested at various times during the oestrous cycle of the rat. Animals were anaesthetized with sodium pentobarbitone, and glass-insulated bipolar platinum electrodes were stereotaxically implanted in the medial preoptic area. The stimulus consisted of accurately balanced biphasic rectangular pulses, height 500 μA, duration 2 ms and frequency 60 Hz, applied in trains of 30 s intervals. The concentration of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in blood samples withdrawn from the external jugular vein immediately before and at frequent intervals up to 1 h after application of the stimulus was determined by radioimmunoassay. In all animals the stimulus was applied for a period of 15 min, for it was found that under these conditions the profiles of LH and FSH produced in individual animals were similar to those which followed the i.v. injection of 50 ng synthetic luteinizing hormone releasing factor (LH-RF)/100 g body wt, the minimal ovulatory dose of LH-RF in our laboratory. Both for LH and FSH, the profiles of responsiveness of the hypothalamo-hypophysial axis to electrical stimulation through the oestrous cycle resembled closely the profile of responsiveness of the anterior pituitary gland to LH-RF administered intravenously. There was a relatively gradual increase in pituitary sensitivity, in terms of the mean maximal increments, between the early afternoon of dioestrus and pro-oestrus, followed by an abrupt and marked rise which reached a peak at 18.00 and 21.00 h of pro-oestrus for LH and FSH, respectively. Sensitivity of the hypothalamo-hypophysial axis declined through oestrus and metoestrus reaching a nadir at 13.30 h of dioestrus. While these results do not exclude a change in sensitivity of the neural component of the hypothalamo-hypophysial axis during the oestrus cycle, they do indicate that the timing and magnitude of changes in sensitivity of the anterior pituitary gland to both endogenous and exogenous LH-RF are similar. This raises the possibility that a marked increase in the secretion of LH-RF during the afternoon of pro-oestrus may not be necessary for the occurrence of the surge of LH and FSH, for conceivably the latter could depend on a change in sensitivity of pituitary gonadotrophs to constant or only slightly increased levels of LH-RF in hypophysial portal blood. Our findings are compared with those of workers who have employed electrochemical stimulation of the preoptic area.

The role of sex steroid hormones in modulating the responsiveness of the anterior pituitary gland to luteinizing hormone releasing factor in the female rat.

SUMMARY The role of ovarian hormones in the development of increased sensitivity of the anterior pituitary gland to synthetic luteinizing hormone releasing factor (LH-RF) which occurs before and during the preovulatory surge of luteinizing hormone (LH) in the rat has been examined. The response of the pituitary gland was determined, with respect to the secretion of LH and follicle-stimulating hormone (FSH), after the intravenous injection of 50 ng LH-RF/100 g body weight. The LH-RF was injected 30–60 min after the administration of sodium pentobarbitone at either 13.30 h or 18.80 h of pro-oestrus. Blood samples were collected immediately before and at frequent intervals after the injection of LH-RF, and the concentration of LH and FSH in these samples was measured by radioimmunoassay. Ovariectomy at 10.00–11.00 h of dioestrus reduced the LH response to LH-RF injected at 14.00 h of pro-oestrus, while oestradiol benzoate administered immediately after ovariectomy restored and even augmented this response. These data together with the finding that administration of the antioestrogen, ICI 46 474, at 17.00 h of dioestrus reduced the LH response to LH-RF injected on the afternoon of pro-oestrus indicates that the initial phase of increased pituitary sensitivity to LH-RF is dependent upon the marked rise in the concentration of oestradiol-17β in plasma which precedes the preovulatory surge of LH. The abrupt, marked increase in pituitary sensitivity to LH-RF, which, in the normal cycle, occurs between 14.00 and 18.30 h of pro-oestrus, failed to develop in rats ovariectomized on the morning of dioestrus whether or not oestradiol benzoate was administered after the operation. However, the LH response to LH-RF injected on the evening of pro-oestrus increased significantly when progesterone was administered at 13.00 h of pro-oestrus in rats ovariectomized and treated with oestradiol benzoate at 10.00–11.00 h of dioestrus. This suggests that the development of the second phase of increased pituitary sensitivity to LH-RF depends, at least partially, on progesterone acting on an oestrogen-primed pituitary gland. The concentrations of FSH in blood samples taken before injection of LH-RF at either 14.00 or 18.30 h of pro-oestrus were significantly greater in ovariectomized compared with those in sham-operated rats. In contrast the FSH responses, in terms of the mean maximal increments, were not significantly different in the various groups irrespective of the nature or time of operation or the time of injection of LH-RF. The FSH response to LH-RF was not appreciably altered by treatment with either oestradiol benzoate or progesterone immediately after ovariectomy although it was increased significantly by the sequential administration of oestrogen and progesterone. The significance of the findings that under certain conditions there were considerable differences between the LH and FSH responses to synthetic LH-RF is discussed with respect to the hypothesis that there is a common releasing factor for both gonadotrophins.

ChemInform Abstract: SYNTHETIC LUTEINIZING HORMONE RELEASING FACTOR, SHORT CHAIN ANALOGS

Chemischer InformationsdienstVolume 5, Issue 25 Natural Products ChemInform Abstract: SYNTHETIC LUTEINIZING HORMONE RELEASING FACTOR, SHORT CHAIN ANALOGS J. RIVIER, J. RIVIERSearch for more papers by this authorM. AMOSS, M. AMOSSSearch for more papers by this authorC. RIVIER, C. RIVIERSearch for more papers by this authorW. VALE, W. VALESearch for more papers by this author J. RIVIER, J. RIVIERSearch for more papers by this authorM. AMOSS, M. AMOSSSearch for more papers by this authorC. RIVIER, C. RIVIERSearch for more papers by this authorW. VALE, W. VALESearch for more papers by this author First published: June 25, 1974 https://doi.org/10.1002/chin.197425447Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume5, Issue25June 25, 1974 RelatedInformation

Effects of exogenous estrogen and progestin on pituitary responsiveness to synthetic luteinizing hormone-releasing factor.

The effect of estrogen and progestin on pituitary responsiveness to 150 mug synthetic luteinizing hormone-releasing factor (LRF) was assessed in premenopausal women receiving sequential (n=12) and combination (n=7) contraceptive steroids. A marked contrast in the time-course and maximal response to LRF was found; a prompt but quantitatively smaller luteinizing hormone (LH) response was seen during cyclic combination therapy, while a delayed (five times) but enhanced (fivefold) LH response was observed during estrogen segments of cyclic sequential therapy. For follicle-stimulating hormone (FSH), the maximum rise was also higher, and the peak response was similarly delayed in the latter group. The quantitative secretion in response to LRF for LH (area under the curve), but not for FSH, was significantly greater (P < 0.01) in subjects receiving sequential, as compared to subjects receiving combination treatment. In both groups, characteristic gonadotropin responses to LRF were reproducible and were independent of the duration of treatment. Since LRF studies were performed during the estrogen segment of treatment cycle in subjects receiving sequential steroids, our data suggest that estrogen exerts a direct feedback action at the pituitary level and that pituitary responsiveness to LRF is augmented by estrogen.

Biphasic Effect of Estrogen on the Sensitivity of the Pituitary to Luteinizing Hormone-Releasing Factor (LRF)

Infusions of synthetic LRF were given in ovariectomized animals, and the effect on plasma concentrations of FSH and LH was determined by radioimmunoassay. Synthetic LRF induced a graded release of LH between doses of 100-2500 ng⁄hr and of FSH with doses of 100 and 500 ng⁄hr of the decapeptide. Peak concentrations were reached at 2 hr in the case of LH and 3 hr in the case of FSH. The relative magnitude of the release of LH was much greater than the magnitude of FSH release. Intravenous injection of 100 ng of estradiol benzoate partially blocked the LH and FSH response to LRF within 1 hr following injection. The inhibitory effect was maximal at 2 hr and had largely disappeared by 4 hr. Injections of 50 or 200 ng of progesterone iv did not modify the responses to LRF infusion. If the infusion of LRF was delayed until 6 hr after the injection of estradiol benzoate, the pattern changed, and there was an enhanced response to LRF, such that plasma LH concentrations were 2½-fold greater in estradiol-treated anim...