Suppression Of Follicle-stimulating Hormone Research Articles

Follicular populations following inhibition of follicle stimulating hormone with equine follicular fluid during early pregnancy in the mare

In two experiments, mares received either charcoal-extracted follicular fluid (treated animals: Experiment 1, n = 6; Experiment 2, n = 6) or saline (control animals: Experiment 1, n = 7; Experiment 2, n = 6). Treatment was given once every 12 h beginning on Day 14 of pregnancy (ovulation = Day 0) and was terminated on Day 30 (Experiment 1) or on Day 41 (Experiment 2). Analysis of follicle stimulating hormone (FSH) concentrations and follicular endpoints were done for Days 14 to 30 (Experiment 1) and Days 14 to 50 (Experiment 2). In both experiments, there was a significant main effect of treatment due to suppressed concentrations of FSH in the treated group. For the follicular endpoints, the means were significantly reduced in the treated group when averaged over all days for the number of follicles 11 to 15 mm (Experiment 2), 16 to 20 mm, >20 mm, and for the diameter of the largest and second largest follicles (both experiments). The depressed follicular activity (diameter of the largest and second largest follicles and the number of follicles for different diameter categories) following follicular fluid treatment supported the hypothesis that follicular development during early pregnancy in the mare is attributable to circulating concentrations of FSH. The administration of follicular fluid and the resulting suppression of FSH and follicular activity did not have a significant effect on concentrations of progesterone or on the maintenance of pregnancy.

Induction of Luteinizing Hormone, Follicle-Stimulating Hormone Surge in the Estrogen-Primed Castrated Male Rat by Progesterone12

Male rats were castrated at 26 days of age and treated with 0.05, 0.1, 1.0 and 2.0 micrograms/kg of BW of estradiol for 4 days starting with the day of castration. On the morning of Day 30 of life they were sacrificed and serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were determined. A significant reduction of LH and/or FSH occurred only with the 1.0 and 2.0 micrograms/kg of BW dose of estradiol. This was in sharp contrast to results in female rats at the same age in which 0.2 microgram/kg of BW of estradiol suppressed the post-castration rise of gonadotropins. This change in threshold sensitivity to the suppressive effects of estradiol may be one component of the changes accompanying the masculinization of the hypothalamus. The 1.0 and 2.0 micrograms/kg of BW doses of estradiol then were used in combination with 0.1, 0.5, 1.0, 2.0, 4.0 and 8.0 mg/kg of BW of progesterone. The addition of progesterone to the treatment regimen resulted in either no change or a suppression or stimulation of FSH and LH, depending upon the dose of progesterone used. With the 2 micrograms/kg of BW dose of estradiol, 1.0 mg/kg of BW of progesterone resulted in a surge of both FSH and LH, irrespective of whether it was given in combination with estradiol or a single injection following 4 days of estradiol treatment. This, to our knowledge, is the first demonstration of a gonadotropin surge induced by progesterone in the estrogen-primed castrated male rat.

Comparison of pharmacodynamic properties of various estrogen formulations

A group of 23 healthy postmenopausal women received one or more 2-week courses of daily administration of the following estrogen preparations: piperazine estrone sulfate (Ogen), 0.3, 0.625, 1.25, 2.5, and 5.0 mg; micronized estradiol (Estrace), 1,2, and 10 mg; conjugated estrogens (Premarin), 0.3, 0.625, 1.25, and 2.5 mg; ethinyl estradiol (Estinyl), 10 and 20 μg; and diethylstilbestrol, 0.1 and 0.5 mg. Each dosage of each formulation was ingested by three women. In those women who received more than one dosage, each course was separated by a drug-free interval of at least 4 weeks. Pretreatment and posttreatment levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), corticosteroid-binding globulin-binding capacity, sex hormone-binding globulin-binding capacity, angiotensinogen, estrone, and estradiol were determined. The relative potency of these five estrogen formulations was determined by parallel line analysis for each of these responses, except LH. On a weight basis, piperazine estrone sulfate and micronized estradiol were equipotent for all responses. Conjugated estrogens suppressed FSH in a fashion equipotent to that of the other nonsynthetic estrogens; however, for all three hepatic parameters, the response was exaggerated twofold to threefold. The synthetic estrogens, diethylstibestrol and ethinyl estradiol, were relatively more potent on a weight basis for every response and produced the most marked response (fourfold to eighteenfold in excess of their FSH suppression) for the hepatic parameters.

Influence of danazol treatment during the luteal phase on pituitary and ovarian function during the subsequent menstrual cycle

Eight subjects with normal menstrual cycles were treated with danazol (800 mg daily) during one luteal phase to assess the effect on follicular development in the subsequent cycle. Plasma levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, and progesterone were measured daily throughout both cycles. Following danazol there was a consistent and significant delay to the preovulatory estradiol (P less than 0.05) and LH (P less than 0.02) peaks and a significant suppression of the early follicular phase FSH (P less than 0.05) and preovulatory estradiol peak plasma levels (P less than 0.05). All other parameters of the post-danazol cycle were indistinguishable from normal. However, there was a small suppression of midluteal phase FSH during danazol treatment, compared with the posttreatment cycle, which was significant for three subjects. It is suggested that the small effect of luteal phase danazol on subsequent follicle development may occur at an intraovarian level through an effect on receptors or enzymes as well as through the small degree of suppression of midluteal phase and early follicular phase FSH.

Effect of testosterone, estradiol-17 beta, and 5 alpha-dihydrotestosterone on inhibin production by sertoli cells in culture.

Inhibin activity in charcoal-extracted spent culture medium of Sertoli cells in Primary culture (CSCCM) was monitored by following the temporal inhibition of serum levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in normal adult male rats. Subcutaneous injection of CSCCM reduced LH and FSH levels within 15 min and maintained the inhibition up to 10 hr. No selective suppression of FSH was observed. The model was used to assess inhibin activity in CSCCM from Sertoli cell cultures incubated with 5 alpha-dihydrotestosterone (DHT), testosterone (T), and estradiol -17 beta (E2) (5 micrograms/ml) for 24 hr. CSCCM from T and E2 treated groups suppressed gonadotropins while the group exposed to DHT failed to elicit any inhibition. DHT seems to inhibit the release of inhibin by Sertoli Cells.

Specific FSH suppression in male rat by porcine follicular fluid

A variety of protocols using intact, castrated, and sham-castrated adult male rats was used to test the ability of porcine follicular fluid to selectively suppress serum follicle-stimulating hormone (FSH). A total dose of 500 microliters follicular fluid injected intraperitoneally will suppress FSH in the rat with testes within 5 h of injection. This is more than is necessary to suppress FSH in the intact or ovariectomized female. A total dose of 1 ml of follicular fluid is needed to suppress FSH reliably in the castrated male rat. Serum FSH is suppressed significantly beginning between 4 and 5.5 h after intraperitoneal injection of 1 ml of follicular fluid and 3 h after intravenous injection. The suppression continues until 10 h postinjection and is abated by 26 h postinjection. Serum luteinizing hormone (LH) is unaffected by follicular fluid in any protocol tested. It is concluded that 1) follicular fluid can suppress serum FSH in the male if large enough doses are given, 2) follicular fluid has no effect on serum LH, and 3) follicular fluid suppresses serum FSH levels in the male as well as previously tried testicular sources. These results suggest that the delay in demonstrating the existence of inhibin may be due to the use of males as both source and test subject.

Effects of Testicular and Ovarian Inhibin‐Like Activity, Using In Vitro and In Vivo Systems

Inhibin‐like activities in charcoal‐treated bovine follicular fluid (FF) and medium from cultured Sertoli cells (SCCM) were assayed in an in vitro bioassay system, using cultured pituitary cells. Addition of both fluids resulted in parallel dose‐dependent decreases of the concentration of follicle‐stimulating hormone (FSH) in the medium, both in the presence or absence of luteinizing hormone‐releasing hormone (LH‐RH).A single injection of FF into immature and adult male and female rats resulted in decreased peripheral levels of FSH, but not of LH, after 4 or 8 h. This decrease was larger and occurred faster in adult female rats than in prepubertal female animals. Injection of FF into adult female rats, immediately after unilateral ovariectomy (ULO) prevented the specific increase of FSH levels, occurring in control animals. This suppression could not be obtained after treatment with steroids.Daily treatment of adult female or immature male rats for periods longer than 5 days did not result in prolonged suppression of circulating FSH concentrations; LH levels were significantly increased. The female animals showed cyclic vaginal smear changes and normal ovulation; in the male rats testis weight and numbers of spermatogenic cells were reduced.It is concluded that testicular and ovarian inhibin‐like activities have similar properties. Injections of FF into male and female rats cause similar effects on FSH and LH. The effect of FF in ULO‐animals suggests that inhibin could play a role in the short‐term regulation of the number of developing follicles in the ovary. Injection of FF into male rats causes a probably transient impairment of spermatogenesis through an initial suppression of FSH.

GONADOTROPIN AND TESTOSTERONE MEASUREMENTS AFTER ESTROGEN ADMINISTRATION TO ADULT MEN, PREPUBERTAL AND PUBERTAL BOYS, AND MEN WITH HYPOGONADOTROPISM

Extract: Nineteen male subjects were given five daily injections of 17β-estradiol and circulating levels of estradiol (E2), testosterone (T), and gonadotropins were determined by radioimmunoassay before, during, and after the steroid course. Peak levels of E2 attained during the 5 days of treatment ranged from 173–577 pg/ml. Four of seven normal adult men and one castrate man demonstrated suppression of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) with a subsequent rise in LH (positive feedback) while E2 levels remained elevated. A rise in T was associated with the LH increment in the four normal men. Nine pre-, early, or midpubertal boys and two men with hypogonadotropic hypogonadism displayed only gonadotropin suppression after E2 administration. The difference in LH response to estrogen (i.e., positive feedback) between the adult men with normal or elevated gonadotropin levels as compared with the endocrinologically normal boys is significant (P < 0.01). Speculation: Positive feedback between estrogen and LH is present in intact adult men, although the magnitude and consistency of this response is less than in women. Testosterone in men may act like progester-one in the female rhesus monkey to blunt the magnitude of the LH rise during estrogen administration. The potential for positive feedback appears to be a maturational event occurring during puberty in men as well as in women.

Further evidence for inhibin: change in serum luteinizing hormone and follicle-stimulating hormone levels after x-irradiation of rat testis.

Department of Medicine, Mount Sinai Hospital and University of Toronto, Toronto, Ontario M5G 1X5, Canada (Received 2 December 1974) It has been postulated that testicular tubules are responsible for the production of a substance, inhibin, which selectively inhibits or modulates the secretion of follicle-stimulating hormone (FSH) by the pituitary gland. Testicular germinal cell depletion such as that seen after chemotherapy for lymphoma resulted in a rise of serum FSH while luteinizing hormone (LH) changed very little or not at all (Van Thiel, Sherins, Myers & De Vita, 1972). In 1968, Paulsen reported that X-irradiation of human testes resulted in germinal cell depletion with a concomitant rise in urinary FSH levels. These studies suggest that germinal cells produce an FSH regulating substance which is lost when germinal tissue is destroyed. Setchell & Jacks (1974) demonstrated that selective FSH suppression could be achieved in male or female rats injected with rete testis

SUPPRESSION OF URINARY AND PLASMA FOLLICLE STIMULATING HORMONE BY EXOGENOUS ESTROGENS IN PREPUBERTAL AND PUBERTAL CHILDREN

Clomiphene citrate, an anti-estrogen with mild estrogenic properties, inhibits rather than stimulates gonadotropin excretion in prepubertal and early pubertal children. These and other data suggest that the sensitivity of the hypothalamic-pituitary gonadostat decreases at the onset of puberty. To test this hypothesis further, the daily excretion of urinary follicle-stimulating hormone (FSH) and luteinizing hormone (LH) was determined in 19 children (5 short normals and 14 with isolated human growth hormone (HGH) deficiency) who were given ethinyl estradiol (EE) 1.4-14.7 mug/m(2) per day (2-10 mug/day) for 4 to 7 days. In addition, plasma and urinary gonadotropins and plasma estrogens were serially determined in two prepubertal females(with isolated HGH deficiency) given two injections (24 h apart) of estradiol benzoate, 10 mug/kg. FSH and LH concentrations in plasma and kaolin-acetone urinary concentrates and plasma 17beta-estradiol (E(2)) and estrone (E(1)) were measured by radioimmunoassays. 2-3 mug/m(2) per day of EE significantly suppressed urinary FSH (and LH when detected in the control period) in two out of six prepubertal children, while all doses >5 mug/m(2) per day suppressed urinary gonadotropins to undetectable levels in eight prepubertal subjects. In early to midpubertal subjects. 2-10 mug/m(2) per day of EE produced a slight suppression of urinary FSH, but failed to suppress to undetectable levels. Two subjects in late puberty (stage 4) did not suppress their urinary FSH while on 7 and 8.3 mug/m(2) per day. In both subjects treated with estradiol benzoate, plasma FSH promptly decreased after the first injection. Urinary FSH was suppressed to <0.1 IU/day on day 2 and urinary and plasma gonadotropins remained suppressed for the duration of the study (3 days). Plasma E(2) and E(1) rose from prepubertal values to peak concentrations of 150 to 250 pg/ml (E(2)), and 50 and 100 pg/ml (E(1)) at approximately 36 h. We conclude that the hypothalamic-pituitary-gonadal axis is operative in the prepubertal child and that the sensitivity of the hypothalamic-pituitary center(s) which control the secretion of FSH and LH decreases at the onset of puberty in man.

Suppression of urinary and plasma follicle-stimulating hormone by exogenous estrogens in prepubertal and pubertal children.

Clomiphene citrate, an "anti-estrogen" with mild estrogenic properties, inhibits rather than stimulates gonadotropin excretion in prepubertal and early pubertal children. These and other data suggest that the sensitivity of the hypothalamic-pituitary "gonadostat" decreases at the onset of puberty. To test this hypothesis further, the daily excretion of urinary follicle-stimulating hormone (FSH) and luteinizing hormone (LH) was determined in 19 children (5 "short normals" and 14 with isolated human growth hormone (HGH) deficiency) who were given ethinyl estradiol (EE) 1.4-14.7 mug/m(2) per day (2-10 mug/day) for 4 to 7 days. In addition, plasma and urinary gonadotropins and plasma estrogens were serially determined in two prepubertal females(with isolated HGH deficiency) given two injections (24 h apart) of estradiol benzoate, 10 mug/kg. FSH and LH concentrations in plasma and kaolin-acetone urinary concentrates and plasma 17beta-estradiol (E(2)) and estrone (E(1)) were measured by radioimmunoassays. 2-3 mug/m(2) per day of EE significantly suppressed urinary FSH (and LH when detected in the control period) in two out of six prepubertal children, while all doses >5 mug/m(2) per day suppressed urinary gonadotropins to undetectable levels in eight prepubertal subjects. In early to midpubertal subjects. 2-10 mug/m(2) per day of EE produced a slight suppression of urinary FSH, but failed to suppress to undetectable levels. Two subjects in late puberty (stage 4) did not suppress their urinary FSH while on 7 and 8.3 mug/m(2) per day. In both subjects treated with estradiol benzoate, plasma FSH promptly decreased after the first injection. Urinary FSH was suppressed to <0.1 IU/day on day 2 and urinary and plasma gonadotropins remained suppressed for the duration of the study (3 days). Plasma E(2) and E(1) rose from prepubertal values to peak concentrations of 150 to 250 pg/ml (E(2)), and 50 and 100 pg/ml (E(1)) at approximately 36 h. We conclude that the hypothalamic-pituitary-gonadal axis is operative in the prepubertal child and that the sensitivity of the hypothalamic-pituitary center(s) which control the secretion of FSH and LH decreases at the onset of puberty in man.

Studies of the role of sex steroids in the feedback control of FSH concentrations in men.

Studies on the role of sex steroids in the feedback control of follicle stimulating hormone (FSH) concentrations in 22-35 year old men are reported. 10 normal volunteers and 8 men undergoing evaluation for azoospermia or oligospermia received steroids by constant infusion for 96 hours at twice the estimated daily production rate of normal men to obtain stable levels in peripheral blood. 15 mg of testosterone increased plasma testosterone and estradiol levels 2-fold and suppressed FSH and luteinizing hormone (LH) approximately 40% during infusion Days 3 and 4. 90 mcg of estradiol/day caused similar suppression of FSH and LH and the addition of 4.5 mg of 17 alpha-hydroxyprogesterone had no additive effect. 7.5 mg of dihydrotestosterone/day produced no detectible changes in FSH or LH. No evidence for a selective effect of any of the steroids on FSH secretion was seen. These data support the concept that although there is a specific seminiferous tubular factor regulating FSH secretion, testicular steroids also modulate FSH secretion.

Suppressed follicle-stimulating hormone (FSH) in women with gestational trophoblastic neoplasms.

Plasma FSH, human chorionic gonadotropin, and estradiol, and urinary FSH and total gonadotropins were measured in eight women with gestational trophoblastic neoplasms. Absolute or relative FSH suppression occurred in 7 of the 8 women when plasma hCG exceeded 50 ng/ml and total urinary gonadotropins were greater than 500 mouse uterine units/24 hr. FSH suppression could not be related to levels of plasma estradiol in all cases.

Serum gonadotropins before, at the inception of, and following human pregnancy.

Serum gonadotropins were determined by radioimmunoassay before at the inception of and following human pregnancy. The subject studied during an ovulatory cycle and ensuing pregnancy was a 21-year-old primiparous female with no abnormalities noted. Also daily levels of luteinizing hormone-human chorionic gonadotropin (LH-HCG) and follicle stimulating hormone (FSH) of a 24-year-old primiparous female were determined from 5 to 74 days after delivery. The results indicated the presence of low FSH levels at the inception of and immediately following pregnancy. The specificity of the FSH radioimmunoassay was suggested by low FSH concentrations in the face of increasingly high HCG levels. The different patterns of FSH and LH (FSH rising and remaining relatively constant prior to the slow rise in LH) suggest that FSH determinations were not influenced by the LH present. Suppression of FSH and the slow return to normal levels of LH following delivery suggest suppression of LH during pregnancy.

Differential Patterns of Release and Suppression of Follicle-Stimulating Hormone and Luteinizing Hormon in Pre- and Postmenopausal Women and in Subjects with Gonadal Disorders.

s1 May 1968Differential Patterns of Release and Suppression of Follicle-Stimulating Hormone and Luteinizing Hormon in Pre- and Postmenopausal Women and in Subjects with Gonadal Disorders.D. S. Schalch, M.D., L. A. Lee, B.S., R. C. Boon, M.D.D. S. Schalch, M.D.Search for more papers by this author, L. A. Lee, B.S.Search for more papers by this author, R. C. Boon, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-68-5-1145_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe simultaneous measurement of changes in plasma follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by radioimmunoassay has revealed distinctly different patterns of release and suppression of these two hormones. This is true in young women during normal menstrual cycles, in postmenopausal women, and in subjects with primary and secondary gonadal disorders treated with estrogen, testosterone, or clomiphene. In five of nine women with normal menstrual cycles, FSH levels (mean values in parentheses) rose markedly both during the follicular phase (8.3 µg/ ml) and at midcycle (10.7 mµg/ml), while LH rose only at midcycle (12.1 mµg/ml). Moderate doses of estrogen only... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Rochester, New York PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByBilateral Adrenalectomy for Advanced Prostatic CarcinomaAntepartum Pituitary Insufficiency in Diabetes MellitusDON S. SCHALCH, M.D., S. ZANE BURDAY, M.D. 1 May 1968Volume 68, Issue 5Page: 1145-1145KeywordsBlood plasmaEstrogensFollicle stimulating hormoneFollicle-stimulating hormoneLuteinizing hormoneMenstrual cycleRadioimmunoassaysTestosterone Issue Published: 1 May 1968 PDF DownloadLoading ...