Plasma Gonadotropin Concentrations Research Articles

Seasonal changes in plasma concentrations of gonadotropins and in the responsiveness of the pituitary and testis to GnRH in a desert rodent, the sand rat (Psammomys obesus)

The male sand rat (Psammomys obesus), captured alive in the Sahara desert in the area of Béni-Abbès (Algeria), exhibited seasonal changes in plasma concentrations of LH, characterized by an increase in early summer. Administration of a standard dose of GnRH (200 ng/100 g body weight) failed to elicit significant season-dependent changes in LH release, whereas the increase in plasma testosterone was maximum in June-July and quite small between November and March-April. The present results suggest that the summer seasonal onset of the testicular endocrine activity of the sand rat is due to increases both in LH release and in testis sensitivity to gonadotropin.

Immunization of merino ewes with a synthetic inhibin peptide or with preparations obtained from bovine and porcine follicular fluids by immunoaffinity chromatography result in different effects on ovulation rate and on plasma gonadotrophin concentrations

Ewes were immunized with either a synthetic peptide (peptide 1-32) that has an amino acid sequence identity with the first 32 amino acids at the amino terminal of the alpha-subunit of porcine inhibin, or with bovine or porcine monoclonal antibody purified inhibin (bMPI and pMPI respectively), obtained by immunochromatography from follicular fluids. The peptide 1-32 was conjugated to albumin before use. Peptide 1-32 and bMPI increased ovulation rate and number of follicles (greater than or equal to 5 mm diameter). Although bMPI increased plasma FSH concentration the peptide did not. pMPI had no effect on ovarian activity but markedly elevated both plasma FSH and LH concentrations. The plasma LH concentration was lowered in ewes immunized with peptide 1-32. It appears, therefore, that ovulation rate can be increased following increased plasma FSH concentrations at luteolysis or in the absence of such an increase. Conversely, greatly increased plasma gonadotrophin concentrations at luteolysis (pMPI) were not followed by an increase in ovulation rate. Antibodies in the plasma of ewes immunized with peptide 1-32 and bMPI bound to iodinated synthetic human inhibin alpha-chain 6-30 peptide. The results suggest that ovulation rate is at least partly determined by intraovarian factors.

The effect of various drugs with neuroendocrine activity and transdermal estradiol on plasma gonadotropin concentrations after ovariectomy in reproductive-aged women

In the present study we compared the effect of different neuroactive drugs with that of estrogen treatment on the ovariectomy-induced plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) changes. A total of 35 menstruating women undergoing ovariectomy were randomly divided into five groups of 7 patients each, receiving a 4-week treatment with oral clonidine, lisuride and sodium valproate, transdermal 17 beta-estradiol, or placebo. The treatment started the day after ovariectomy. Surgery was done during the early follicular phase of the cycle. Blood samples were collected before and after 3, 5, 7, 14, 21 and 28 days of treatment. During the treatment, hot flushes were subjectively recorded. The placebo-treated group showed a progressive increase in plasma LH and FSH concentration during the month following ovariectomy. The same changes occurred in the lisuride and sodium valproate treated groups. Plasma LH levels in ovariectomized women treated with clonidine showed an increase which was higher than in placebo-treated women (p less than 0.01), while FSH levels were similar to those in the placebo group. In the estradiol-treated group the increase in both gonadotropins was significantly less (p less than 0.01) than in the placebo group. The frequency and intensity of hot flushes were high in placebo and sodium valproate treated subjects, being significantly reduced by clonidine, lisuride and estrogen treatment. Our results seem to indicate that clonidine treatment modulates the LH postcastration rise and that both neuroendocrine and gonadal mechanisms influence the changes in the activity of the GnRH-pituitary axis following ovariectomy.

The GnRH pulse generator

The notion of an oscillator or signal generator in the central nervous system that controls the rhythmic release of GnRH and, thereby, the pulsatile secretion of the gonadotropic hormones, originated in the finding of strikingly abrupt and rhythmic fluctuations in the concentration of LH in the plasma of ovariectomized monkeys. These oscillations had a period of about one hour when blood samples were obtained at 10 to 20 minute intervals. I These surprising observations were presaged by reports of seemingly random, major fluctuations in plasma gonadotropin concentrations in gonadectomized and rats1 as well as in women.' In these earlier studies the sampling intervals employed were never less than one hour and unable, therefore, to reveal the orderly, rhythmic events that occur with frequencies of one event per hour, or more. In the original study describing pulsatile LH secretion in ovariectomized monkeys the possibility was considered that the circhoral discharges of LH may be initiated by autoregulatory mechanisms involving long or short feedback loops, but the more likely view that these discharges were due to intermittent signals from the central nervous system unrelated to circulating LH levels that resulted in putative increments in GnRH release was favored. Nevertheless, the possible role of autoregulatory mechanisms in the control of pulsatile LH secretion was repeatedly considered,6 but finally laid to rest in the relatively recent past.7 Conversely, the view that each pulse of LH released from the pituitary gland is the consequence of a bolus of GnRH secreted into the pituitary portal system has been unequivocally upheld by the demonstration of synchronous increments ofGnRH assessed in the pituitary portal circulation and of LH measured in samples of peripheral blood obtained simultaneously.s, 9 In any case, the phenomenon of pulsatile gonadotropic hormone secretion was rapidly extended to most vertebrate species studied in this regard, including our own, and

STIMULATION OF GONADOTROPIN SECRETION IN PREPUBERTAL MONKEYS AFTER HYPOTHALAMIC EXCITATION WITH ASPARTATE AND GLUTAMATE*

To test the hypothesis that aspartate (Asp) and glutamate (Glu) can be used to probe the functional integrity of the GnRH neuron, the dose-response relationships between i.v. administered, endogenously occurring amino acids (Asp and Glu) and GnRH release were determined in the prepubertal male monkey. GnRH release was assessed indirectly by monitoring the LH response by the pituitary, the sensitivity of which had been heightened by prior exposure to pulsatile GnRH. Four of these animals received an i.v. bolus of 0, 1.5, 4.8, 15, 48 and 150 mg/kg BW of each of the amino acids. Plasma gonadotropin and amino acid concentrations were measured immediately before and for 3 hours after administration of Asp and Glu. The 150 mg/kg dose of both amino acids resulted in a dramatic rise in plasma LH concentrations that peaked at 10 min after injection. At this dose plasma Asp and Glu levels increased 200-fold and 50-fold, respectively. No significant LH release was seen with any of the lower doses. These results indicate that i.v. administration of these acidic amino acids in prepubertal monkeys stimulates GnRH release. Based upon this observation, we hypothesize that Asp or Glu could be used to develop a clinical test of GnRH neuronal function.

黒毛和種供卵牛における血漿中の性腺刺激ホルモン,卵巣ステロイドホルモンおよびインヒビン濃度と採卵成績との関係

過剰排卵処理牛(供卵牛)における血漿中のLH, FSH, inhibin, progesterone (P4)およびestradiol-17β(E2)濃度と採卵成績(排卵数,正常卵数)との関係を調べた.供卵牛は排卵数(推定黄体数=CL; Group I:CL≦9, Group I':CL≧10)と正常卵数(NE) (Group II:NE=0,Group II':NE≧1)でグループ(群)分けして検討した.その結果,以下のことが示唆された,1)排卵数が多い群(CL≧10)では,処理開始時の血漿中のインヒビン,E2濃度およびE2/P4比が低い傾向がみられた.2) 排卵数が多い群では,発情時のLHサージは低く,FSHサージは低くなる傾向がみられた.逆にインヒビン濃度は高く,E2濃度は高くなる傾向がみられた.3) 正常卵が得られなかった群(NE=0)は,発情時のインヒビンおよびE2濃度が高く,LHおよびFSHサージは低い値を示した.4) 発情時のE2の濃度と排卵数の間には,有意な相関が見られなかったが,インヒビン濃度と排卵数の間に正の相関(r=0.54, P<0.05)が見られた.従って,卵胞の発育数や排卵数のモニターにインヒビンの測定が有効であると考えられる.

Ovarian control of gonadotrophin secretion in the prepubertal heifer

In order to investigate the development of ovarian feedback control of gonadotrophin secretion in the immature animal, three groups of eight Hereford X Friesian heifers were bilaterally ovariectomized at either 2, 6 or 12 weeks of age. Blood samples were collected for gonadotrophin analysis (15-min intervals for 6 h) on days −1, 4, 7, 14, 28, 55 and 110 relative to ovariectomy. The ovaries from these animals showed that follicular development was established soon after birth and the follicles were producing oestradiol. In all animals, ovariectomy was followed by a rise in plasma gonadotrophin concentrations although the response was delayed in heifers ovariectomized at 2 weeks compared to those ovariectomized at 6 or 12 weeks of age. Mean LH concentrations were significantly elevated 14, 7 or 4 days after ovariectomy and mean FSH concentrations were significantly higher than pre-treatment values 28, 7, or 4 days post-ovariectomy in heifers ovariectomized at 2, 6 or 12 weeks of age, respectively. The results suggest that an inhibitory mechanism, of ovarian origin, that controls gonadotrophin secretion develops between 2 and 12 weeks of age in the heifer.

Differences in the plasma concentrations of FSH and LH in ovariectomized Booroola FF and ++ ewes

During 12 sampling days before ovariectomy the mean plasma FSH but not LH concentrations in FF ewes were higher (P less than 0.01) than those in ++ ewes (16 ewes/genotype). After ovariectomy increases in the concentrations of FSH and LH were noted for ewes of both genotypes within 3-4 h and the rates of increase of FSH and LH were 0.18 ng ml-1 h-1 and 0.09 ng ml-1 h-1 respectively for the first 15 h. From Days 1 to 12 after ovariectomy, the overall mean +/- s.e.m. concentrations for FSH in the FF and ++ ewes were 8.1 +/- 0.6 and 7.1 +/- 0.4 ng/ml respectively and for LH they were 2.7 +/- 0.3 and 2.1 +/- 0.2 ng/ml: these differences were not statistically significant (P = 0.09 for both FSH and LH; Student's t test). However, when the frequencies of high FSH or LH values after ovariectomy were compared with respect to genotype over time, significant F gene-specific differences were noted (P less than 0.01 for both FSH and LH; median test). In Exp. 2 another 21 ewes/genotype were blood sampled every 2nd day from Days 2 to 60 after ovariectomy and the plasma concentrations of FSH and LH were more frequently higher in FF than in ++ ewes (P less than 0.01 for FSH and LH). The F gene-specific differences in LH concentration, observed at 21-36 days after ovariectomy were due to higher mean LH amplitudes (P less than 0.025) but not LH peak frequency in FF than in ++ ewes.(ABSTRACT TRUNCATED AT 250 WORDS)

The Nature of the Defect in Familial Male Pseudohermaphroditism in Arabs of Gaza*

Studies in six Arab individuals from Gaza with familial male pseudohermaphroditism (MPH) due to 17-ketoreductase deficiency revealed several metabolic aberrations associated with the disorder. Plasma LH, FSH, testosterone, and androstenedione concentrations were low in the two prepubertal patients. After hCG administration plasma androstenedione increased markedly. The four postpubertal MPH patients had very high plasma gonadotropin and androstenedione concentrations, the latter increasing further after hCG administration. Plasma testosterone concentrations in all six patients were moderately low or normal for age and increased little after hCG administration. Spermatic venous testosterone concentrations, measured in three adults, were within the normal range in two and low in one, while androstenedione concentrations were markedly elevated (15- to 32-fold) in all three patients. Kinetic analyses of progesterone and androstenedione metabolism were performed in testicular tissue of these patients and compared to the results in two control subjects. While testicular tissue from the two prepubertal patients metabolized progesterone only to androstenedione, and that to a limited extent, the tissue from the four postpubertal patients metabolized progesterone to 16 alpha- and 16 beta-hydroxyprogesterone, 17 alpha-hydroxyprogesterone, androstenedione, and testosterone and metabolized androstenedione to testosterone. The Michaelis constants of these reactions were similar in the tissue from the MPH and the control subjects. The production of 16 alpha- plus 16 beta-hydroxyprogesterone was 5.4- to 10.3-fold greater, and 17-hydroxylase activity was 5.8- to 8.1-fold lower in the testes of the postpubertal MPH patients compared to values in the control subjects. The preference of androstenedione production through the delta 4- or delta 5-pathways was examined in the testes of two adult MPH patients using an equimolar concentration of [14C]progesterone and [3H]pregnenolone as substrates. While the flow of substrates in the control testes was equal or slightly greater through the delta 4-pathway, the delta 5-pathway predominated in the testes of the MPH patients. A large amount of dehydroepiandrosterone accumulated when NAD, the cofactor for 3 beta-hydroxysteroid dehydrogenase-isomerase, was omitted, supporting the contention that androstenedione was produced in the testes of the MPH patients mainly through the delta 5-pathway. Additional support for this suggestion was the finding that the 3H/14C ratio in androstenedione and testosterone produced from both substrates was 8 times higher in the testes from MPH patients than in those from the control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma gonadotropin and progesterone concentrations during the estrous cycle of Finn, Suffolk and Targhee ewes

Hormonal profiles during the estrous cycle of Finn, Suffolk and Targhee ewes were compared in six ewes of each breed. Blood samples were drawn by venipuncture at 8-h intervals from onset to onset of consecutive estrous periods. Number of corpora lutea (CL) and ovarian follicles ≥3 mm in diameter on Day 10 (estrus = Day 0) were observed using endoscopy. Estrous cycle length was 14.9, 15.6 and 16.4 d (P<0.01) in Finn, Suffolk and Targhee ewes, respectively. Finns had more (P<0.001) CL (3.5) than Suffolks (2.0) and Targhees (1.8), but luteal phase progesterone concentrations were similar among breeds in peak level and area under the curve. In Finn ewes, the amplitude of the preovulatory LH surge was lower (P<0.01) and tended to occur later in estrus; otherwise LH levels and patterns were similar among breeds. A coincident follicle stimulating hormone (FSH) preovulatory surge occurred in most ewes, the amplitude of which was related to that of luteinizing hormone (LH); r = 0.67, P<0.01. Plasma FSH levels and patterns were similar in Finn, Suffolk and Targhee ewes and most ewes had three to four secretory episodes. Follicles ≥3 mm averaged 1.8, 1.0 and 1.2 (P>0.1) in Finn, Suffolk and Targhee ewes, respectively. Results indicate that the higher ovulation rate of the Finn ewe is not elicited by increased FSH levels at any stage of the estrous cycle.

Characteristics of flutamide action on prostatic and testicular functions in the rat

The effect of daily treatment with the pure antiandrogen Flutamide has been studied either alone or in combination with the LHRH agonist [ d-Trp 6, des-Gly-NH 10 2]LHRH ethylamide (LHRH-A), on testicular and prostatic functions in adult male rats. Treatment for 10 days with Flutamide (5 mg/rat, twice daily) caused a marked stimulation of plasma testosterone (T) associated with a significant increase in plasma gonadotropin concentrations and inhibited plasma PRL levels. Testicular weight is not changed following antiandrogen administration but testicular LH/hCG receptor levels are markedly decreased with no change in FSH receptor levels. Moreover, Flutamide treatment alone produces an important inhibition of ventral prostate and seminal vesicle weights associated with a significant decrease in prostatic β-adrenergic receptor levels but no change is observed in specific ornithine decarboxylase (ODC) activity. Daily LHRH-A treatment at the dose of 1 μg/day for 10 days decreases plasma T to levels comparable to those found in orchiectomized men (0.30 ± 0.5 ng/ml). This effect is associated with an almost complete loss of testicular LH/hCG receptors, a decrease in testicular weight, a significant increase in plasma gonadotropins and a marked inhibition of plasma PRL concentration. A relatively smaller inhibition of ventral prostate and seminal vesicle weights follows treatment with the LHRH agonist alone, this effect being accompanied by a significant reduction in β-adrenergic receptor concentration but no change in prostatic ODC activity. Combination of the two drugs, however, caused a potent inhibitory effect on both ventral prostate and seminal vesicle weight to values similar to those found in castrated rats. The prostatic weight loss is accompanied by a marked fall in ODC activity and in the concentration of β-adrenergic receptors. The present data clearly show that combined treatment with an LHRH agonist and a pure antiandrogen is highly effective in inhibiting, not only prostatic growth, but also two androgen-sensitive parameters of prostatic activity.

Plasma gonadotrophin concentrations, pituitary gonadotrophin content and pituitary responsiveness to LHRH in rats treated with LHRH and oestradiol benzoate

Suppression of gonadotrophin secretion during prolonged treatment with a high dose of LHRH was studied. Long-term ovariectomized rats were infused for 6 days with various doses of LHRH (25, 50, 100, 250 or 500 ng/h) with or without simultaneous treatment with oestradiol benzoate (OB; 3 micrograms/s.c. injection); a further group was treated with OB only. The effects of these treatments were studied on plasma concentrations of LH and FSH, the pituitary content of LH and FSH and on LH and FSH secretion in vitro (perifusion) in the unstimulated state and following maximal LHRH stimulation (1 microgram LHRH/ml perifusion medium). Administration of LHRH caused a dose-dependent reduction in plasma concentrations of LH and FSH and depleted the pituitary LH/FSH stores. Treatment with OB lowered the plasma concentration of LH to about 30% and that of FSH to about 65% of the control values. Administration of OB plus a low dose of LHRH (25 or 50 ng/h) markedly stimulated the secretion of LH but not of FSH, so that the plasma concentrations of LH were fully restored to the control value. With higher rates of LHRH infusion, OB caused no enhancement of the plasma concentrations of LH and FSH. The experiments in vitro revealed a sensitizing, i.e. stimulatory effect, of OB on LHRH-stimulated LH and FSH secretion. However, the higher the rate of infusion of LHRH the smaller the sensitizing effect. Interpolation from dose-response curves showed that an LHRH infusion rate of about 150 ng/h (which would establish a plasma concentration of LHRH of about 68 pmol/l) would have no effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Different gonadotropin pulsatile fashions in anovulatory cycles of young girls indicate different maturational pathways in adolescence.

To characterize the spectrum of pulsatile gonadotropin secretion during the postmenarchal period, we studied 24 adolescents whose gynecological age was 1-4 yr. Six women with ovulatory cycles formed a control group. Eighteen women with anovulatory cycles were grouped on the basis of mean plasma LH values: group 1 (n = 8) with high LH values and group 2 (n = 10) with normal LH values. In all women, plasma gonadotropin concentrations were measured at 10-min intervals for 8 h on day 4 of the cycle. Pulsatile gonadotropin secretion was also studied a second time in 7 women from group 1 and 7 from group 2 after 5 days of progesterone (P) in oil treatment to assess the role of P in regulating gonadotropin secretion in the postmenarchal period. Group 1 had more frequent and greater LH pulses than the other two groups (which were very similar) and had the highest plasma 17 beta-estradiol, testosterone (T), androstenedione (A), and 17-hydroxyprogesterone concentrations. In all anovulatory women, basal LH values were correlated with the LH interpulse interval (r = -0.65; P less than 0.01) and pulse amplitude (r = 0.86; P less than 0.001). LH pulse amplitude was correlated with basal 17 beta-estradiol values (r = 0.74; P less than 0.001), and LH interpulse interval with basal T (r = -0.83; P less than 0.001), A (r = -0.51; P less than 0.05), and 17-hydroxyprogesterone (r = -0.79; P less than 0.001) values. P administration decreased LH pulse frequency and increased LH pulse amplitude more in group 2 than in group 1 with high LH values; a clear reduction was also found in A, T, and 5 alpha-dihydrotestosterone values. These results indicate that 1) anovulatory young women with high plasma LH values have an alternative maturational pathway, different from that of anovulatory women with normal plasma LH values, who are similar to ovulatory adolescents; 2) the pulsatile pattern of gonadotropin secretion has specific roles linked separately to amplitude and frequency in controlling ovarian steroidogenesis, which accounts for the endocrine differences between groups; and 3) in the postmenarchal period, by modulating LH and FSH pulsatility and thus reducing androgen levels and their atretic action on follicles, P may be a basic regulatory factor in enhancing functional cyclicity.

Ontogeny of Gonadotropin Secretion in Congenital Anorchism: Sexual Dimorphism Versus Syndrome of Gonadal Dysgenesis and Diagnostic Considerations

The hormonal characteristics of anorchism are elevated basal levels of gonadotropins, especially follicle-stimulating hormone and a low concentration of plasma testosterone that fails to increase after the administration of human chorionic gonadotropin. However, little is known about the dynamics of plasma gonadotropin secretion in infants and children with anorchism. We analyzed plasma gonadotropin concentrations and their responses to luteinizing hormone releasing factor, along with plasma testosterone responses to human chorionic gonadotropin, in 9 children with surgically proved bilateral anorchism. Basal concentrations of gonadotropins, especially plasma follicle-stimulating hormone, are elevated above normal during the first 3 to 4 years of life, decrease gradually to normal prepubertal levels and then increase again after age 9 years. This age-dependent diphasic pattern of gonadotropin secretion is comparable to that described previously in patients with the syndrome of gonadal dysgenesis and it is consistent with steroid-independent central nervous system inhibition of pulsatile luteinizing hormone releasing factor secretion during mid childhood. Moreover, a sex difference in follicle-stimulating hormone and luteinizing hormone values was observed; the mean follicle-stimulating hormone and luteinizing hormone concentrations in anorchid boys less than 3 years old were lower than in patients with Turner’s syndrome. We suggest that this sex dichotomy is a consequence, at least in part, of the actions of testosterone derived from the fetal testis on the fetal hypothalamus.Luteinizing hormone releasing factor administration to anorchid male subjects resulted in an age-dependent augmented release of gonadotropin, particularly follicle-stimulating hormone. This study emphasizes that the age of the patient must be considered when interpreting basal gonadotropin levels. We also propose that in mid childhood the luteinizing hormone releasing factor test in conjunction with the human chorionic gonadotropin stimulation test is a more accurate hormonal indicator of patients with congenital anorchism than either the human chorionic gonadotropin test or basal gonadotropin concentrations. (J. Urol., 138: 587–591, 1987)

A quantitative study of steroid bioconversions in the testis of the African catfish, Clarias gariepinus (Burchell), under natural spawning and natural and cultivated non-spawning conditions.

Quantitative aspects of bioconversions in the testes of the African catfish (Clarias gariepinus) were studied in vitro by incubation of tissue with [3H]pregnenolone or [3H]androstenedione. During the breeding period, spawning and non-spawning animals were collected from their natural habitat, the Hula nature reserve, in northern Israel. In the same period, non-spawning animals were collected from a fish pond in the same region. It was shown that spawning was accompanied by significant changes in steroid bioconversions, i.e. a reduction in androgen synthesis, especially of 11 beta-hydroxyandrostenedione and 11 beta-hydroxytestosterone and an increase in the production of C21-steroids, especially progesterone, 17 alpha-hydroxyprogesterone and a pregnenolone ester. These changes resulted from a decreased contribution of the cytochrome P-450 enzymes 17 alpha-hydroxylase, C17-20-lyase and 11 beta-hydroxylase. A rise in plasma gonadotrophin concentration was observed only in spawning catfish. In the absence of such an increase in plasma gonadotrophin, steroid synthesis in the testes of non-spawning feral and pond catfish was primarily directed towards the production of 11-oxygenated androgens and 5 beta-pregnane-3 alpha,17 alpha,20 alpha-triol. It is suggested that spawning is induced by gonadotrophin and the ensuing change in steroidogenesis. It is possible that husbandry conditions inhibit the necessary increase in gonadotrophin release.

Ovarian responses in macaques to pulsatile infusion of follicle-stimulating hormone (FSH) and luteinizing hormone: increased sensitivity of the maturing follicle to FSH.

This study investigated the relationship between plasma gonadotropin concentrations and the initiation and maintenance of preovulatory follicular growth in macaques. Eight adult cynomolgus monkeys were treated with a GnRH antagonist [AcD2Nal1-4ClDPhe2, DTrp3, DArg6, DAla10]GnRH X HOAc to block endogenous gonadotropin secretion. In four animals, a pulsatile infusion of human FSH and human LH (hLH) (one 3-min pulse/h) was initiated, and the amount of hFSH delivered per pulse was increased every 3-4 days until serum estradiol concentrations rose. Thereafter, the amount of FSH delivered per pulse was reduced by 12.5%/day for 5 days, whereas the amount of LH delivered per pulse was not altered. Results indicated that plasma FSH concentrations in the range of 15-20 mIU/ml were associated with the initiation of estrogen production; in addition, a progressive reduction in plasma FSH concentration to 8-10 mI/ml over the subsequent 5 days was accompanied by continued rises in estradiol concentrations and preovulatory follicular growth. In contrast, in four control animals, maintenance of plasma FSH concentrations at 8-10 mIU/ml for 13 days did not result in elevation in serum estradiol concentrations or antral follicular growth. These observations demonstrate that after stimulation by elevated FSH concentration, follicles can continue to mature in the presence of FSH concentrations which are unable to support the growth of less mature follicles. Thus, this may account for the mechanisms by which the maturing follicle continues to develop during the mid-through late follicular phase of the menstrual cycle, whereas other less mature follicles undergo atresia.

Characterization of the physiological pattern of episodic gonadotropin secretion throughout the human menstrual cycle.

To characterize the spectrum of pulsatile gonadotropin secretion during the course of the normal menstrual cycle, we studied normal women during 51 ovulatory cycles. Plasma gonadotropin concentrations were measured at 10-min intervals for 20-24 h during the early, mid-, and late follicular phases and the early, mid-, and late luteal phases. LH data series were analyzed using 2 different computer-assisted algorithms for pulse detection. The LH interpulse interval decreased during the follicular phase (FP) from 94 +/- 4 (+/- SEM) min in the early FP (EFP) to 71 +/- 4 min by the late FP (LFP; P less than 0.001). The estimation of LH pulse frequency in the EFP was significantly affected by slowing of episodic LH secretion during sleep. In the luteal phase (LP), the LH interpulse interval progressively increased from 103 +/- 8 min in the early LP (ELP) to 216 +/- 39 min by the late LP (LLP; P less than 0.001). Sleep-associated slowing of episodic LH secretion also occurred in the ELP. The mean LH pulse amplitude in the EFP (6.5 +/- 0.4 mIU/ml) decreased significantly by the midfollicular phase (MFP; 5.1 +/- 0.8 mIU/ml; P less than 0.05) and increased once again by the LFP (7.2 +/- 1.2 mIU/ml). LH pulse amplitude was highest in the ELP (14.9 +/- 1.7 mIU/ml), decreased by the midluteal phase (MLP) to 12.2 +/- 2.0 mIU/ml, and declined further by the LLP to 7.6 +/- 1.1 mIU/ml (P less than 0.001 vs. ELP). FSH secretion was significantly (P less than 0.05) correlated with LH secretion at time lags of 0-10 min in 82% of the studies. These results indicate the following. 1) In the EFP and ELP, the frequency of gonadotropin pulsations is reduced at night in association with sleep. 2) The frequency of LH secretion increases from the EFP to MFP and LFP. 3) LH pulse amplitude decreases in the MFP, suggesting enhanced negative feedback of estrogen on the hypothalamic-pituitary axis and/or a decrease in GnRH secretion at this stage. 4) A progressive reduction of LH pulse frequency and amplitude occurs during the LP which is correlated with the duration of exposure of the hypothalamic-pituitary axis to progesterone. 5) A close relationship exists between secretion of LH and FSH, suggesting a common stimulatory factor for both gonadotropins.

Plasma concentrations of gonadotrophins, preovulatory follicular development and luteal function associated with bovine follicular fluid-induced delay of oestrus in heifers.

In Exp. 1, injections of 10 ml bovine follicular fluid (bFF, i.v. or s.c.), given twice daily for 3 days after injection of a luteolytic dose of PGF-2 alpha, delayed the onset of oestrus in 3 of 6 heifers to 8 or 9 days after PGF-2 alpha, as compared with 2 or 3 days after PGF-2 alpha in control heifers. Mean plasma concentrations of FSH and LH during the injection period were not different from those in saline-injected heifers. In Exp. 2, i.v. injections of 20 ml bFF twice daily for 3 days uniformly delayed oestrus to 8 days after PGF-2 alpha (N = 4) and injections of 20 ml bFF i.v. every 6 h for 24h on the day of PGF-2 alpha injection delayed oestrus to 5.0 +/- 0.6 days after PGF-2 alpha as compared with 2.8 +/- 0.3 days for control heifers. In both treatment groups, plasma concentrations of FSH were suppressed during the injection period and increased transiently after treatment, but plasma concentrations of LH during the injection period were not different from those of control heifers. Plasma levels of oestradiol in heifers given bFF remained basal for 2 or 3 days after treatment, then increased several days before the delayed oestrus, in a manner similar to that in control heifers, and elicited normal preovulatory surges of LH and FSH. Plasma concentrations of progesterone and the length of the next oestrous cycle were normal, indicating formation of functional corpora lutea. Therefore, bFF treatments appear to delay oestrus by selectively suppressing plasma FSH, without affecting LH, and delaying the development of the preovulatory follicle. These results suggest that FSH may be critical to support the growth and development of the preovulatory follicle after luteolysis in cows.

Plasma gonadotrophin and ovarian steroid concentrations in women with menstrual cycles with a short luteal phase.

Daily plasma concentrations of FSH, LH, oestradiol-17 beta and progesterone were compared for 12 cycles with a short luteal phase and 19 cycles with a luteal phase of normal length (i.e. cycles in which the luteal phase lasted 12 or more days). FSH and LH concentrations were suppressed in short luteal-phase cycles in the early follicular phase and the length of the follicular phase was prolonged (median duration, 14.5 days, range 13-21 days: compared with 12 days, range 9-17, in control cycles; P less than 0.025). Preovulatory oestradiol-17 beta values and the mid-cycle concentrations of FSH and LH were similar in both groups. Plasma progesterone values in the luteal phase were similar in both groups over the 2nd to 5th days inclusive after the midcycle LH peak but declined in the short luteal phases thereafter. In short luteal-phase cycles, menstruation occurred in the presence of higher levels of oestradiol-17 beta and progesterone than in cycles of normal length and the rise of gonadotrophin in the late luteal phase of the cycle was delayed. These findings suggest that in cycles with a short luteal phase there is a lack of synchrony between the ovarian and menstrual events.

A Study of the Role of the Postnatal Testes in Determining the Ontogeny of Gonadotropin Secretion in the Male Rhesus Monkey (Macaca mulatto)*

To further examine the role of the testes in determining the ontogeny of gonadotropin secretion in the male rhesus monkey, the time courses of circulating LH and FSH concentrations were determined using established RIAs in daytime and nighttime blood samples collected at weekly intervals from birth until 4 yr of age in intact animals (n = 7) and in males orchidectomized at approximately 1 week of age (n = 6). Estimates of plasma androgen (A) concentrations were obtained on nonchromatographed samples with a RIA that reacts with testosterone and other androgens. Plasma PRL concentrations were also determined by RIA, and body weight was monitored at weekly intervals. Testicular volumes were measured at weekly intervals after 1.8 yr of age in five animals. In intact animals, mean daytime plasma A concentrations during the first 3 months of infantile development ranged from 1-6 ng/ml. Daytime plasma A concentrations then declined to reach 0.5-1 ng/ml by 9 months of age, where they were maintained usually until 3 yr of age when circulating levels progressively increased to reach, by approximately 3.5 yr of age, mean levels (6 ng/ml) characteristic of fully mature males. During the transition from infantile to perpubertal development, circulating LH and FSH concentrations showed a pattern similar to that of A, with elevations during the first 2 months of life followed by a decline to undetectable concentrations. In contrast to A, however, distinct pubertal increments in circulating LH and FSH concentrations were not observed in daytime samples from intact animals. The first indication of the pubertal reactivation of the hypothalamic-pituitary-testicular axis was provided by a reemergence of nocturnal elevations in plasma A concentrations between 2-3 yr of age. These were followed shortly thereafter by detectable plasma LH concentrations in nighttime samples. Orchidectomy at 1 week of age resulted in a progressive and dramatic rise in circulating gonadotropin concentrations, which plateaued approximately 3 weeks later at values 1 order of magnitude greater than those observed in intact animals. This hypersecretion of LH and FSH was not sustained, however, and by 10 months of age, plasma gonadotropin concentrations in agonadal animals were indistinguishable from those in age-matched intact controls. These low levels of the gonadotropic hormones were maintained, in the absence of the testes, for approximately 2 yr until a second or "pubertal" postcastration hypersecretion of LH and FSH was observed.(ABSTRACT TRUNCATED AT 400 WORDS)