Relationship between follicle-stimulating hormone, androstenedione and oestradiol in human follicular fluid

The concentrations of FSH, oestradiol and androstenedione in the follicular fluid of normal and cystic human follicles were measured at different stages of the menstrual cycle. In addition, the number of granulosa cells in the follicles was determined. In follicles in which FSH was detectable, the concentration of oestradiol was greater than that of androstenedione, irrespective of the stage of the cycle. In contrast, in those follicles in which FSH was undetectable and in all cystic follicles irrespective of the level of FSH, the concentration of androstenedione was greater than that of oestradiol. In follicles containing FSH there was a highly significant linear correlation between the number of granulosa cells and the concentration of follicular oestradiol (P less than 0.001). It is suggested that in human ovaries up to 90% of the oestradiol in follicular fluid may originate from the granulosa cells.     

Plasma concentrations of luteinizing hormone, follicle-stimulating hormone and progesterone during the breeding season in ewes immunized against androstenedione or testosterone

Levels of plasma LH, FSH and progesterone during the breeding season were measured by radioimmunoassay in control ewes and ewes actively immunized against androstenedione-11 alpha-hemisuccinyl--bovine serum albumin or testosterone-3(O-carboxymethyl)oxime--bovine serum albumin. Immunization against androstenedione resulted in normal oestrous cycles with raised plasma LH and progesterone levels and a reduction in the concentration of FSH during the luteal phase. It is tentatively suggested that androstenedione, or its metabolites, could modify the oestrogenic control of LH secretion and facilitate the release of FSH in the ewe. Immunization against testosterone prevented oestrus and resulted in markedly increased levels of LH without alteration of the FSH concentration. Since evidence of increased binding of oestradiol-17 beta was found in the ewes immunized against testosterone, these results cannot be attributed solely to a reduction in the biologically active faction of testosterone.     

Effect of exposure to the altitude of 300 meters below sea-level on testosterone, luteinizing hormone, follicle-stimulating hormone and prolactin in man

Serum testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin (PRL) responses to exposure to sea-level altitude (LA) were examined in 13 eugonadal males, age 21-22 yr, 3 and 5 days after residing at LA and on the second day of return to basal altitude 90 days later. After 3 days at their respective residence altitude, there was elevation in LH (p less than 0.05) and depression in testosterone levels (p less than 0.05), with similar results on day 5. These effects were all of transient nature, LH and testosterone concentrations returned to their basal levels on second day of the return to basal altitude. The FSH and PRL levels did not show any significant change during the stay at LA or after return to basal altitude. The observations suggest that exposure to LA is associated with increase in plasma levels of LH and decrease in testosterone. The decreased levels of testosterone could be due to a reduction in the sensitivity of the testis to LH, or due to inhibition of steroidogenesis in the testis.     

Studies on the pattern of circulating steroids in the normal menstrual cycle. I. Simultaneous assays of progesterone, pregnenolone, dehydroepiandrosterone, testosterone, dihydrotestosterone, androstenedione, oestradiol and oestrone.

In an attempt to analyze the multiple changes and interactions in circulating steroid levels in the peri-ovulatory and peri-menstrual periods, the plasma levels of immunoreactive luteinizing hormone (LH), progesterone and unconjugated pregnenolone, dehydroepiandrosterone, testosterone, oestradiol and oestrone were assayed daily during a complete cycle in 17 normally menstruating women. In 14 of the 17 subjects studied androstenedione and unconjugated dihydrotestosterone were also estimated. The day of the LH-peak and the first day of menstruation, respectively, were used to synchronize the peri-ovulatory and peri-menstrual plasma levels of the various steroids. With the exception of dehydroepiandrosterone and dihydrotestosterone, the plasma levels of all steroids exhibited significant, but different changes during the cycle. Testosterone levels showed a slight but significant increase around the LH-peak, whereas the levels of pregnenolone and androstenedione were higher in the post-ovulatory than in the pre-ovulation periods. The levels of oestradiol and oestrone, as well as the ratios of oestradiol to oestrone gradually increased from the low values observed in the early proliferative phase to pre-ovulatory peak values. The relationship between peaks of oestradiol and oestrone and that of LH exhibited great individual variation. The same was true for the individual oestradiol to oestrone ratios. The combination of several steroidal signals did not improve the predictive value of the analyses. However, an increase of individual progesterone values by at least 0.35 ng/ml from the day preceding the LH-peak to the day of the LH-peak was observed in 13 of the 17 subjects. It is suggested that for the early detection of the LH surge and prediction of the subsequent ovulation daily assays of plasma progesterone are of more value than the assay of the other steroids investigated.     

Effects of oestradiol and progesterone on pulsatile secretion of luteinizing hormone in ovariectomized ewes

The effect of treatment with oestradiol, progesterone, a combination of the two steroids or no steroids on pulsatile release of luteinizing hormone (LH) was examined in ovariectomized ewes. Beginning 3 days after ovariectomy, 5 ewes were assigned to each of the following treatment groups: 0.7 mg oestradiol, 16 mg progesterone, 0.7 mg oestradiol plus 16 mg progesterone or no steroid. All treatments were administered twice daily for 3 weeks in a 0.5 ml injection of ethanol given sc. After 2 weeks of treatment and 1, 4, 8, 16 and 32 days after the treatment period ended, blood samples were obtained from all ewes at 10-min intervals for a 6-h period. At the end of the 6-h period, 100 micrograms gonadotrophin-releasing hormone (GnRH) was injected iv and blood samples were collected at 15 min intervals for an additional 5 h to estimate the relative pituitary content of LH. Ovariectomized ewes receiving no steroid presented regular pulses of LH at frequency of four to five pulses during a 6-h sampling period. Treatment with progesterone alone decreased the frequency of pulsatile release of LH to approximately 1 pulse/6 h, but did not affect the amplitudes of the pulses of LH. Recovery of pulsatile release of LH to a frequency of four or five pulses of LH in a 6-h period was complete between 16 ewes. Oestradiol, administered alone or with progesterone, resulted in a decrease in both the frequency and the amplitude of pulses of LH compared to control ewes and a decrease in GnRH-induced release of LH.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma concentrations of luteinizing hormone and follicle-stimulating hormone during anoestrus in ewes actively immunized against oestradiol-17 beta, oestrone or testosterone

The concentrations of LH and FSH in jugular venous plasma were measured during anoestrus in control ewes and ewes actively immunized against 17 beta-oestradiol-6-(O-carboxymethyl)oxime--bovine serum albumin, oestrone-6-(O-carboxymethyl)oxime--bovine serum albumin or testosterone-3-(O-carboxymethyl)oxime--bovine serum albumin. During a 12 h sampling period, the basal level of LH and the frequency of LH pulses were significantly increased in all the immunized animals. The plasma FSH concentration was increased in two out of five oestradiol-immunized ewes and two out of three oestrone-immunized animals. The plasma FSH concentration in the testosterone-immunized animals was similar to the control values. Significant titres of antibodies to oestradiol-17 beta were found in all the immunized animals. It is suggested that binding of oestradiol-17 beta in the circulation by antibodies reduced the negative feedback action normally eserted by this steroid on LH secretion and, to a lesser extent, on FSH escretion. However, since the oestradiol antibody titres in the testosterone-immunized and oestrone-immunized ewes were considerably lower than those found in the oestradiol-immunized animals, it is possible that testosterone and oestrone, perhaps by acting as prehormones, could influence the negative feedback control by oestradiol-17 beta of gonadotrophin secretion in the anoestrous ewe.     

Changes in the plasma concentrations of luteinizing hormone, progesterone, oestradiol and testosterone and in the binding of follicle-stimulating hormone to the theca of follicles during the ovulation cycle of the hen (Gallus domesticus)

The changes in the binding of FSH during follicular maturation were examined in the hen using 125I-labelled bovine FSH (bFSH) and unlabelled bFSH. The binding of 125I-labelled bFSH was not inhibited by bovine LH or chicken LH but was inhibited by extracts of chicken pituitary glands. The ovarian stroma, which contained both interstitial tissue and small follicles, bound the greatest amount of FSH. As the follicles progressed through the yolk-filled hierarchy of maturation, they bound decreasing amounts of FSH. In the two largest follicles of the hierarchy, there was a significant increase in the binding of FSH 12-16h before ovulation. There were two peaks in the concentrations of LH; a preovulatory peak occurred 4-6h before ovulation and a second peak occurred 14-16h before ovulation. Plasma concentrations of testosterone, oestradiol and progesterone began to rise 9, 8 and 6h, respectively, before ovulation. These data are consistent with the hypothesis that changes in the gonadotrophin concentration and binding regulate the order of the follicular hierarchy and the onset of preovulatory steroidogenesis in the hen.     

Regulation of plasma oestrogens in normal adult males. II. Response of oestradiol, oestrone, testosterone and cortisol to dexamethasone and ACTH administration.

The response of plasma oestradiol (Oe-2), oestrone (Oe-1), testosterone (T) and cortisol to dexamethasone and ACTH administration in normal adult males was ascertained. After an oral dose of 1.5 mg dexamethasone Oe-1 decreased from 2. 51 to 1.85 ng/100 ml (74% of the control level, mean of 15 subjects) over night and after continuing the dexamethasone administration for two more days (twice daily 1.5 mg) Oe-1 decreased to 1.30 ng/100 ml (52%). Oe-2 (control level 1.71 ng/100 ml) and T (678 ng/100 ml) did not change over night, but at the end of the test Oe-2 decreased to 84% and T to 91% of the control level. After a single im injection of 2 mg beta 1-24 cortrophin Oe-1 increased 1.9 times (meanof 13 subjects) without further increase during two more days of treatment (twice daily 1 mg), while Oe-2 did not change over night and decreased to 75% of the control level at the end of the test. Under ACTH T decreased to 66% of the control level over night and to 50% at the end of the test indicating a suppression of the testicular hormone secretion. From these results and those reported previously it was concluded that the testicular hormone secretion influences mainly Oe-2 in peripheral plasma, while Oe-1 depends mainly on the adrenal hormone secretion.     

Simultaneous production of monoclonal antibodies to dehydroepiandrosterone, oestradiol, progesterone and testosterone

Mice were immunized with a mixture of four steroid antigens: dehydroepiandrosterone (DHA), oestradiol, progesterone and testosterone linked to bovine serum albumin through the 7, 6, 11 alpha and 17 beta positions respectively. The response to immunization varied widely with no one mouse producing an optimal response to all four steroids. In the two fusion experiments performed, antibodies to all four antigens were developed. Data are presented which show that the immune response of the spleen donor is related to the relative numbers and quality of the antibodies produced to each steroid. Despite the structural identity of the progesterone and testosterone haptens, antibodies elicited in response to their respective antigens could readily be distinguished from each other. From the large number of monoclonal antibodies obtained those most useful for radioimmunoassay were three high affinity antibodies to oestradiol and two antibodies raised against DHA but with high affinity for DHA sulphate.     

Effect of recombinant inhibin on luteinizing hormone and follicle-stimulating hormone secretion in the rat

We investigated the effect of the iv injection of recombinant human (rh) inhibin on FSH and LH secretion in the female rat under various experimental circumstances. Rh inhibin caused dose-related decreases in mean plasma FSH, but not LH, levels in ovariectomized female rats 14 days old and older. The duration of this inhibition was proportional to the dose of rh inhibin, but no consistent changes in FSH secretion were observed until 4 h after treatment. Maximum suppression of FSH release was observed at about 15 micrograms rh inhibin/kg BW and lasted 8-10 h. Measurement of the area under the curve from 4-12 h after injection of inhibin indicated a dose-related decrease in total FSH secreted. When blood samples were withdrawn every 10 min to evaluate pulsatile gonadotropin release, analysis of FSH pulse parameters indicated that rh inhibin (25 micrograms/kg) interfered with pulse frequency, amplitude, and peak levels in both intact and ovariectomized rats. In contrast, pulsatile LH secretion was not measurably altered. These results demonstrate that rh inhibin acts primarily at the level of the pituitary to inhibit all parameters of FSH secretion and suggest that this effect is at least not entirely mediated by changes in GnRH receptors.     

Effect of luteinizing hormone releasing hormone on plasma levels of luteinizing hormone, oestradiol and testosterone in the male dog.

An injection of luteinizing hormone releasing hormone (LH-RH) increased plasma LH and testosterone concentrations in the male dog, but no significant increase in plasma oestradiol-17beta levels was observed. Repeated injections of LH-RH produced an increase in plasma LH levels but there was a progressive decline in the response with each injection. The concentration of plasma testosterone reached a maximum within 40 min of the first injection of LH-RH and remained constant thereafter while plasma oestradiol concentration gradually increased with successive injections of LH-RH.     

Disruption of the joint synchrony of luteinizing hormone, testosterone, and androstenedione secretion in adolescents with polycystic ovarian syndrome

The present study explores the postulate that the polycystic ovarian syndrome (PCOS) is marked by failure of physiological feedforward and feedback signaling between pituitary LH and ovarian androgens. To this end, we appraised the 3-fold simultaneous overnight release of LH (assayed by high precision immunofluorometry), testosterone (RIA), and androstenedione (RIA) in 12 an- or oligoovulatory adolescents with PCOS (mean +/- SEM age, 16.4 +/- 0.47 yr) and 10 eumenorrheic girls (age, 16.5 +/- 0.45 yr). Gynecological (postmenarchal) ages (years) were also comparable at 4.8 +/- 0.39 (PCOS) and 4.0 +/- 3.6 (control; P = NS). Body mass index and fasting serum insulin and estradiol concentrations were indistinguishable in the two study cohorts. Mean overnight serum concentrations of LH (assayed by both immunofluorometry and Leydig cell bioassay), testosterone, androstenedione, and 17alpha-hydroxyprogesterone were each elevated significantly in patients with PCOS (all P 相似文献   

Effects of testosterone, FSH, and LH on oestradiol and progesterone secretion by preovulatory cumulus oophorus complexes of the rat.

Female Wistar rats exhibiting a regular 4-day oestrous cycle were included in this study. They were killed in succession on the day of pro-oestrus at 11.00, 18.00, and 22.00 h. From ovarian preovulatory follicles cumulus oophorus complexes (COCs) were isolated and subsequently cultured with or without testosterone (T), T plus FSH, or T plus LH. In control cultures COCs isolated at all investigated hours released similar amounts of oestradiol. T stimulated this basal secretion and the effect was usually enhanced in the presence of FSH or LH. In control cultures the amount of released progesterone was greatest when expanded COCs were isolated (22.00 h). T present in culture media diminished the amount of secreted progesterone. However, when T was added with FSH or LH a distinct stimulatory effect was observed, except in cultures with T plus FSH set up at 22.00 h. Previously, gonadotrophins alone did not effect progesterone secretion. The results suggest that T can regulate steroid, and especially progesterone secretion by COCs. Until the preovulatory gonadotrophin surge T can inhibit luteinization of COCs, while afterwards, acting synergestically with gonadotrphins (especially with LH), T can stimulate progesterone production in the cumulus granulosa cells.     

Seasonal pattern of leutinizing, follicle-stimulating hormone, testosterone and progesterone in adult population of both sexes in the Jordan Valley

Differences were observed in hormonal levels between in both sexes of people living in Irbid City (620 meters above sea level) and in the Jordan Valley (360 meters below sea level). In addition, exercise was shown to differentially affect hormonal levels of both sexes at the above and below sea level locations. Serum levels of leutinizing hormone (LH) and testosterone (T) in adult male and serum levels of follicle-stimulating hormone (FSH) and progesterone (P) in adult female people were investigated in Irbid City and in the Jordan Valley during the years 1997 and 1998. The levels of these hormones were followed each month during this period. In males living in Irbid City, LH and T peaked from March through June, and in females at the same site, FSH and P also peaked from March through June. These data confirm the seasonal variation in sex hormones reported elsewhere in (wo)man and in other species. In males and females of the Jordan Valley, serum levels of LH, FSH, T and P were all higher than those of Irbid City throughout the year. Additionally, peaks of LH and T in male and FSH and P in female subjects in the Jordan Valley were observed from March through September. The high levels of these hormones and the extension of their peaks are suggested to be due to effects of the environmental factors of the Jordan Valley (high temperature, high barometric pressure) compared to those in Irbid City and other areas located at above sea level altitude.     

Diurnal rhythms of luteinizing hormone, follicle-stimulating hormone, testosterone, and estradiol secretion before the onset of female puberty in short children

To investigate hormonal changes before the onset of female puberty, we measured LH and FSH in serum samples drawn every 20 min for 24 h and measured testosterone and estradiol hourly for 24 h. Seventeen girls (13 prepubertal and 4 early pubertal) of short stature, from 5.1-11.4 yr of age, participated in this study. LH and FSH were measured using a time-resolved immunofluorometric assay, and testosterone and estradiol were measured using a sensitivity RIA capable of detecting testosterone and estradiol concentrations of 10 and 2 pg/mL, respectively. Diurnal rhythms of LH, FSH, and testosterone were apparent in all subjects, including those aged 5-6 yr. Serum LH and FSH concentrations showed night-day variation in a pulsatile fashion. The serum testosterone concentration was elevated in the early morning in all subjects. The serum estradiol concentration was elevated in the early morning in 4 of 13 prepubertal subjects and all 4 early pubertal subjects. The diurnal pattern of the serum estradiol concentration was similar to that of the serum testosterone concentration. Mean 24-h LH and testosterone concentrations in prepubertal subjects who did not attain puberty for at least 1 yr were 0.07 U/L and 65 pg/mL, respectively, whereas those in prepubertal subjects who attained puberty within 1 yr (0.14 U/L and 106 pg/mL, respectively) were significantly higher. Furthermore, mean 24-h LH, FSH, testosterone, and estradiol concentrations increased with the onset of puberty. In conclusion, the diurnal rhythms of LH, FSH, and testosterone already exist at 5-6 yr of age, and serum LH and testosterone levels increase before the onset of puberty. These results suggest that preparation for the onset of female puberty may begin in 5- to 6-yr-old girls.     

Dynamic response to follicle-stimulating hormone of secretion of progesterone by superfused rat ovarian granulosa cells

Granulosa cells from immature female rats, pretreated with pregnant mare's serum gonadotropin, were cultured with microcarrier beads for 24 h, and superfused with culture medium. Progesterone was transiently released following a 10-min pulse of FSH (100 ng/ml), and there was a self-priming effect of FSH. 10-min pulses of 8-bromo-adenosine 3',5'-cyclic monophosphate (8Br-cAMP) (1 mg/ml) mimicked the effects of follicle-stimulating hormone (FSH). Continuous superfusion with FSH induced biphasic secretion of progesterone, which was composed of a parabolic (the first) and a plateau (the second) phase. By contrast, the pattern of secretion induced by continuous superfusion with 8Br-cAMP was monophasic. FSH-stimulated secretion of progesterone was rapidly inhibited by the addition of 10 microM cycloheximide (CX), but secretion recovered upon removal of this inhibitor. In the second phase, the recovery of secretion was accompanied by an overshoot of the plateau value. The present results suggest that: (1) the generation of the time-related biphasic pattern of secretion cannot be interpreted by cAMP alone; (2) FSH stimulates the secretion of progesterone by a mechanism that involves newly synthesized protein.     

Differential regulation of gonadotropin secretion by testosterone in the human male: absence of a negative feedback effect of testosterone on follicle-stimulating hormone secretion

Studies of sex steroid regulation of gonadotropin secretion in the human male have focused primarily on the respective site(s) of negative feedback of testosterone (T) and estradiol (E(2)). The use of pharmacological doses of sex steroids in these studies has precluded conclusions about the relative roles of T and E(2) in gonadotropin feedback. Thus, the aims of the present study were to 1) determine the relative contributions of T vs. E(2) to the sex steroid component of gonadotropin regulation, and 2) distinguish the feedback effects of T that that are direct (i.e. mediated by the androgen receptor) vs. indirect (mediated by aromatization to E(2)). Two experimental interventions were used: 1) inhibition of aromatization by a selective aromatase inhibitor to examine the impact of selective E(2) withdrawal; and 2) acute medical castration to examine the effect of ablating both T and E(2). Sixteen normal (NL) men (mean age, 30.5 +/- 2.2 yr) were studied. Nine NL subjects were treated with the aromatase inhibitor, anastrozole (10 mg, orally, daily, for 5 days). Twelve NL men underwent medical castration with ketoconazole (1-g loading dose followed by 400 mg, orally, four times a day for 5 days). Ketoconazole-treated subjects received concomitant treatment with dexamethasone (0.5 mg twice daily) to prevent the development of adrenal insufficiency. Single blood samples were drawn daily between 0800-1000 h. To ensure that dexamethasone was not altering the gonadotropin response to sex steroid ablation by a direct pituitary effect, five GnRH-deficient men (mean age, 37.6 +/- 3.9 yr) underwent GnRH dose-response studies at baseline and after treatment with dexamethasone (0.5 mg twice daily). Aromatase blockade caused significant lowering of E(2) (33 +/- 3 to 14 +/- 1 pg/mL; P: < 0.0005) with a corresponding increase in T levels (563 +/- 42 to 817 +/- 81 ng/dL; P: < 0.05). Treatment with ketoconazole resulted in equivalent suppression of E(2) (41 +/- 4 to 14 +/- 1 pg/mL; P: < 0.0005), but also induced castrate levels of T (491 +/- 28 to 40 +/- 3 ng/dL; P: < 0.0005). Both treatment regimens were associated with a significant increase in gonadotropin levels. For LH, the percent increase in serum levels after castration was almost 3-fold greater than that seen after selective E(2) withdrawal (275 +/- 23% with ketoconazole vs. 95.6 +/- 21% with anastrozole; P: < 0.005). Despite the divergent changes in T levels with these two maneuvers (a marked decrease after ketoconazole and a significant increase with anastrozole), the percent rise in FSH levels was similar in the two protocols (91 +/- 6% vs. 71 +/- 7%, respectively; P: = NS). Inhibin B levels were unchanged after selective E(2) withdrawal (156 +/- 23 vs. 176 +/- 19 pg/mL), but decreased slightly with ketoconazole (156 +/- 15 to 131 +/- 11 pg/mL; P: < 0.05). In contrast to the effects of glucocorticoid administration on gonadotropin secretion in women, no significant changes were observed in the GnRH-deficient men treated with dexamethasone in terms of mean LH levels (19.8 +/- 3.2 vs. 23.3 +/- 5.4 IU/L), mean LH pulse amplitude after GnRH (16.0 +/- 2.5 vs. 19.0 +/- 5.1 IU/L), or mean FSH levels (8.0 +/- 1.9 vs. 9.2 +/- 2.4 IU/L, pre vs. post). These studies provide evidence of differential regulation of gonadotropin secretion by T in the human male. T exerts both direct and indirect feedback on LH secretion, whereas its effects on FSH appear to be mediated largely by aromatization to E(2). From these data we conclude that in terms of sex steroid feedback, E(2) is the predominant regulator of FSH secretion in the human male.