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PubMed1987

The effects of aging in normal men on bioavailable testosterone and luteinizing hormone secretion: response to clomiphene citrate.

Serum testosterone (T) levels in men decline with age while serum LH levels, as measured by RIA, increase. To assess if the decline in serum T levels in healthy aging men is paralleled by an age-related decline in the bioavailable non-sex hormone-binding globulin (SHBG)-bound fraction of T and to determine whether there are age-related changes in LH secretion or LH control of T production, we studied 29 young (aged 22-35 yr) and 26 elderly (aged 65-84 yr) healthy men. All men had single random blood samples drawn, and 14 men in each age group underwent frequent blood sampling for 24 h, both before and after 7 days of clomiphene citrate (CC) administration. Both mean 24-h serum total T levels and non-SHBG-bound T were reduced in elderly men compared to those in young men (P less than 0.05), while estradiol and SHBG levels were similar in the 2 age groups. Serum FSH determined by RIA and LH by RIA and bioassay were higher in the elderly men compared to those in young men (P less than 0.05), but the ratios of LH bioactivity to immunoreactivity and the LH pulse frequency and amplitude were similar. After CC administration, mean serum total T and non-SHBG-bound levels in young men increased by 100% and 304%, respectively, while in older men these values increased by only 32% and 8%, respectively. However, CC-stimulated LH pulse characteristics and serum levels of estradiol, SHBG, FSH, and bioactive and immunoreactive LH were similar in the 2 groups. Thus, both at baseline and after CC stimulation, elderly men had significantly lower serum total T and non-SHBG-bound (bioavailable) T levels than did young men, despite similar or increased levels of bioactive LH and similar bioactive to immunoreactive LH ratios and LH pulse characteristics. These results suggest that major age-related changes in the hypothalamic-pituitary-testicular axis occur at the level of the testes and are manifested by decreased responsiveness to bioactive LH. Administration of CC to young and elderly men resulted in similar changes in LH pulse characteristics and LH bioactivity and immunoreactivity, suggesting preserved hypothalamic-pituitary responsiveness in the elderly.

Adult↗
PubMed1988

Clomiphene citrate attenuates hyperprolactinemia associated with ovarian hyperstimulation in the primate menstrual cycle.

Exogenous human menopausal gonadotropin (hMG) therapy produces transient hyperprolactinemia during ovulation induction or ovarian hyperstimulation for in vitro fertilization, and hyperprolactinemia has been linked to decreased fertility. Coadministration of clomiphene citrate (CC) with hMG is often used to decrease the total amount of hMG used in such patients, but whether this results in less hyperprolactinemia is not known. As the hyperprolactinemia in this setting is a threshold phenomenon dependent on the strength and duration of estrogen exposure, we investigated whether CC acted as an estrogen to enhance PRL secretion or as an antiestrogen deterring estradiol (E2)- and progesterone (P4)-induced hyperprolactinemia in nonhuman primates. Normally cycling (control) monkeys (n = 4) received E2 benzoate (12.5 micrograms/kg, im, daily) on menstrual cycle days 6-33 and continuous crystalline P4 via Silastic implants on days 20-33, a regimen known to initiate hyperprolactinemia. Treated monkeys (n = 5) received the same regimen, except that oral CC (15 mg daily) was given on days 6-33. Daily serum samples were assayed for E2, P4, and PRL. Both treatments caused significant (P less than 0.05) increases in serum PRL concentrations during P4 administration. The CC-treated monkeys had significantly smaller increases in mean PRL [21 +/- 1.5 (+/- SEM) vs. 44 +/- 6.3 ng/mL (micrograms/L); P less than 0.05] and smaller mean area under the PRL response curve [288 +/- 35 (+/- SEM) vs. 588 +/- 121 ng/day.mL (micrograms/day.L); P less than 0.05] than the control monkeys. We conclude that CC attenuates the hyperprolactinemia response to E2/P4 synergy in monkeys by acting as an antiestrogen. If coadministered with hMG for ovulation induction or ovarian hyperstimulation for in vitro fertilization, CC should attenuate hMG-induced hyperprolactinemia, thereby reducing its potentially adverse effects on fertility.

Animals↗
PubMed1989

Enhanced preovulatory progesterone levels in clomiphene citrate-induced cycles.

We measured basal body temperature, cervical mucus, follicular diameter, and serum LH, FSH, 17 beta-estradiol, and progesterone daily in 40 spontaneous ovulatory cycles in 27 infertile women and in 40 clomiphene citrate-induced ovulatory cycles in 31 women. The cervical score was significantly lower and the serum FSH, LH, and 17 beta-estradiol levels were significantly higher during the follicular phase in induced compared with spontaneous cycles. Serum progesterone was significantly higher on the 3 days preceding ovulation and the day of ovulation in the induced cycles. These increased preovulatory serum progesterone levels could contribute to the lower cervical mucus score in the induced compared with spontaneous cycle, whereas their effect on the endometrium is still unclear.

Adult↗
PubMed1997

Urinary follicle-stimulating hormone for normogonadotropic clomiphene-resistant anovulatory infertility: prospective, randomized comparison between low dose step-up and step-down dose regimens.

A low dose step-up and step-down regimen for induction of ovulation using urinary FSH was compared in a prospective randomized fashion in 37 normogonadotropic clomiphene-resistant oligo- or amenorrheic infertile women. The objectives was to assess potential differences in duration of treatment, ovarian stimulation (serum FSH levels), and response [serum estradiol (E2) levels and number and size of follicles]. Monitoring (blood sampling and transvaginal sonography) took place on the day of initiation of treatment, the first day of ovarian response as assessed by ultrasound (i.e. the first day a follicle > or = 10 mm could be recognized), the day of hCG administration to induce ovulation, and 3 days thereafter. The median duration of treatment in the low dose step-up group was 18 (range, 7-41) days compared to 9 (range, 4-16) days in the step-down group (P = 0.003), and the total numbers of ampules administered were 20 (range, 7-69) and 14 (range, 7-33), respectively (P = NS). Serum FSH levels from the first day of sonographic ovarian response until the administration of hCG were constant (median increase, 2%/day) in patients receiving the low dose step-up protocol, but showed a decrease (median, 5%/day) in step-down cycles (P < 0.001). Monofollicular growth, defined as not more than one follicle 16 mm or larger on the day of hCG administration, was observed in 56% of low dose step-up and 88% of step-down cycles (P = 0.04). The percentage of patients with normal range periovulatory E2 serum levels (500-1500 pmol/L) was 33% in the low dose step-up group vs. 71% in the step-down group (P = 0.03). We conclude that a step-down protocol for gonadotropin induction of ovulation exhibits a more physiological, late follicular phase FSH serum profile than a low dose step-up protocol. This results in a shorter duration of treatment, a greater number of monofollicular cycles, and more cycles with periovulatory E2 levels within the normal range in the step-down protocol.

Adult↗
PubMed1998

Predictors of patients remaining anovulatory during clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility.

The diagnostic criteria used to identify patients suffering from polycystic ovary syndrome remain controversial. The present prospective longitudinal follow-up study was designed to identify whether certain criteria assessed during standardized initial screening could predict the response to ovulation induction with clomiphene citrate (CC) in 201 patients presenting with oligomenorrhea or amenorrhea and infertility. Serum FSH levels were within the normal range (1-10 IU/L), and all patients underwent spontaneous or progestin-induced withdrawal bleeding. Initial CC doses were 50 mg daily for 5 days starting on cycle day 3. In the case of an absent response, doses were increased to 100 and 150 mg daily in subsequent cycles. First ovulation with CC was used as the end point. After a complete follow-up (in the case of a nonresponse, at least 3 treatment cycles with daily CC doses up to 150 mg), 156 patients (78%) ovulated. The free androgen index (FAI = testosterone/sex hormone-binding globulin ratio), body mass index (BMI), cycle history (oligomenorrhea vs. amenorrhea), serum androgen (testosterone and/or androstenedione) levels, and mean ovarian volume assessed by transvaginal sonography were all significantly different (P < 0.01) in responders from those in nonresponders. FAI was chosen to be the best predictor in univariate analysis. The area under the receiver operating characteristics curve in a multivariate prediction model including FAI, BMI, cycle history, and mean ovarian volume was 0.82. Patients whose ovaries are less likely to respond to stimulation by FSH due to CC treatment can be predicted on the basis of initial screening characteristics, such as FAI, BMI, cycle history (oligomenorrhea or amenorrhea), and mean ovarian volume. These observations may add to ongoing discussion regarding etiological factors involved in ovarian dysfunction in these patients and classification of normogonadotropic anovulatory infertile women.

Adult↗
PubMed1998

Decline in insulin-like growth factor I levels after clomiphene citrate does not correct hyperandrogenemia in polycystic ovary syndrome.

It is widely accepted that the action of clomiphene citrate (CC) is mediated through its antiestrogenic properties on the hypothalamic-pituitary axis. Although insulin-like growth factor I (IGF-I) enhances the thecal cell response to LH, and estrogen treatment is associated with a reduction in IGF-I levels, CC is known to decrease circulatory IGF-I levels in polycystic ovary syndrome (PCOS) patients. The impact of lowering IGF-I levels on androgen levels in PCOS is unknown. This study was designed to examine the impact of CC treatment on the interrelationships of IGF-I, androgens, and estrogens in normal subjects and patients with PCOS. IGF-I, gonadotropin, androgen, estrogen, and sex hormone-binding globulin levels were measured in 8 PCOS patients and 10 normal subjects before and after treatment with the antiestrogen CC. Studies were performed in the early follicular phase, days 4-6 of the menstrual cycle in normal subjects. In normal subjects, CC treatment led to a significant increase in estradiol (84 +/- 10 to 234 +/- 62 pmol/L, untreated and CC treated; P < 0.05) and estrone (125 +/- 14 to 257 +/- 29 pmol/L; P < 0.05) levels with a significant lowering of IGF-I levels (297 +/- 25 to 230 +/- 17 micrograms/L; P < 0.05). Similarly, in PCOS patients a significant increase in estradiol (110 +/- 11 to 245 +/- 58 pmol/L; P < 0.05) and estrone (301 +/- 32 to 401 +/- 90 pmol/L; P < 0.05) levels and a significant lowering of IGF-I levels (330 +/- 43 to 214 +/- 27 micrograms/L; P < 0.05) were observed after CC treatment. However, no significant correlation was observed between changes in IGF-I and changes in estradiol in either group. Compared to pretreatment levels, no significant changes in the following parameters were observed after 5 days of CC treatment in either study group: testosterone, testosterone/sex hormone-binding globulin ratio, and androstenedione. The relationship among CC treatment, gonadotropin, estrogen, and IGF-I levels is complex. Changes in blood IGF-I levels are not associated with changes in androgen levels, although paracrine and or autocrine effects cannot be excluded.

Adult↗
PubMed1999

Predictors of chances to conceive in ovulatory patients during clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility.

The present prospective follow-up study was designed to identify whether clinical, endocrine, or ultrasound characteristics assessed by standardized initial screening of normogonadotropic oligo/amenorrheic infertile patients could predict conception in 160 women who reached ovulation after clomiphene citrate (CC) medication. Additional inclusion criteria were total motile sperm count of the partner above 1 million and a negative history for any tubal disease. Daily CC doses of 50 mg (increasing up to 150 mg in case of absent ovarian response) from cycle days 3-7 were used. First conception (defined as a positive urinary pregnancy test) was the end point for this study. A cumulative conception rate of 73% was reached within 9 CC-induced ovulatory cycles. Patients who did conceive presented more frequently with lower age (P < 0.0001) and amenorrhea (P < 0.05) upon initial screening. In a univariate analysis, patients with elevated initial serum LH concentrations (>7.0 IU/L) had a higher probability of conceiving (P < 0.01). In a multivariate analysis, age and cycle history (oligomenorrhea vs. amenorrhea) were identified as the only significant parameters for prediction of conception. These observations suggest that there is more to be gained from CC ovulation induction in younger women presenting with profound oligomenorrhea or amenorrhea. Screening characteristics involved in the prediction of ovulation after CC medication in normogonadotropic oligo/amenorrheic patients (body weight and hyperandrogenemia, as shown previously) are distinctly different from predictors of conception in ovulatory CC patients (age and the severity of cycle abnormality). This disparity suggests that the FSH threshold (magnitude of FSH required for stimulation of ongoing follicle growth and ovulation) and oocyte quality (chances for conception in ovulatory cycles) may be differentially regulated.

Adult↗
PubMed2000

Free androgen index and leptin are the most prominent endocrine predictors of ovarian response during clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility.

We have previously demonstrated that obese hyperandrogenic amenorrheic women are less likely to ovulate after clomiphene citrate (CC) medication. The present study was designed to identify whether additional endocrine screening characteristics, all potentially involved in ovarian dysfunction in 182 normogonadotropic oligoamenorrheic infertile women, are associated with ovarian response, which may improve overall prediction of CC-resistant anovulation. Standardized endocrine screening took place before initiation of CC medication (50 mg/day; increasing doses up to 150 mg/day if required) from cycle days 3-7. Screening included serum assays for fasting insulin and glucose, insulin-like growth factor I (IGF-I), IGF-binding protein-1 (IGFBP-1), IGFBP-3, free IGF-I, inhibin B, leptin, and vascular endothelial growth factor. Forty-two women (22% of the total group) did not ovulate at the end of follow-up (a total number of 325 cycles were analyzed). Fasting serum insulin, insulin/glucose ratio, IGFBP-1, and leptin were all significantly different in univariate analyses (P < or = 0.02), comparing CC responders vs. nonresponders. Forward stepwise multivariate analyses in combination with factors reported earlier for prediction of patients remaining anovulatory after CC revealed a prediction model including 1) free androgen index (FAI = testosterone/sex hormone-binding globulin ratio), 2) cycle history (oligomenorrhea or amenorrhea), 3) leptin level, and 4) mean ovarian volume. These data suggest that decreased insulin sensitivity, hyperandrogenemia, and obesity, all associated with polycystic ovary syndrome, are prominent factors involved in ovarian dysfunction, preventing these ovaries from responding to stimulation by raised endogenous FSH levels due to CC medication. By using leptin instead of body mass index or waist to hip ratio, the previous model for prediction of patients remaining anovulatory after CC medication could be slightly improved (area under the curve from 0.82-0.85). This may indicate that leptin is more directly involved in ovarian dysfunction in these patients. The capability of insulin and IGFBP-1 to predict patients who remain anovulatory after CC disappears when FAI enters into the model due to a significant correlation between FAI and these endocrine parameters. This suggests that markers for insulin sensitivity (e.g. IGFBP-1 and insulin) are associated with abnormal ovarian function through its correlation with androgens, whereas leptin is directly involved in ovarian dysfunction.

Adult↗
PubMed1988

Clomiphene therapy in epileptic women with menstrual disorders.

We studied the effects of clomiphene therapy on seizure frequency in 12 women who had clinical and EEG features of complex partial seizures as well as menstrual disorders with reproductive endocrine abnormalities. Ten of the 12 women improved (p less than 0.05); all ten developed normal cycles. The two women who did not improve continued to have irregular prolonged cycles. Average monthly seizure frequency for the entire group declined by 87% (p less than 0.01). Both complex partial and secondary generalized seizures decreased. During the investigation, one unwanted pregnancy occurred, two women developed severe abdominal pain with ultrasound-documented ovarian cysts, and three experienced breast tenderness and pelvic cramps.

Adult↗
PubMed1977

Correlation between rises of gonadotrophins and rises of sex steroids during clomiphene test in men.

Serum FSH, LH and testosterone and urinary excretion of androsterone, aetiocholanolone, dehydroepiandrosterone and total oestrogens were measured in normal and oligospermic men before and after clomiphene stimulation. Responses in all parameters were highly variably from one individual to another and this great variation formed the basis for investigating the correlations between responses. There was no correlation between increase of FSH and LH or increase of LH and steroids. Also there was no correlation between rises of FSH and rises of androgens. But a significant correlation existed between rises of FSH and rises of oestrogens. This confirms that one action of FSH is to stimulate production of testicular oestrogens which presumably takes place in the Sertoli cells.

Adolescent↗
PubMed1981

Clomiphene stimulation test in men with idiopathic hypospermatogenesis.

A standardized clomiphene stimulation test with assay of serum FSH, LH, testosterone and oestradiol and urinary androsterone + aetiocholanolone, dehydro-epiandrosterone and total oestrogens was applied to 23 men with idiopathic hypospermatogenesis as compared with 12 normal controls. In the patients the percentual rise of LH was increased and the percentual rise of testosterone and oestradiol decreased as compared with controls. The study thus showed that abnormalities in the testicular steroid producing apparatus exist in hypospermatogenesis and could be the cause of the spermatogenetic failure. It was further showed that the reserve capacity of the testicular steroid production is highly limited in contrast to the large reserve capacity of gonadotrophin production in the hypophysis.

Adult↗
PubMed1984

Characterization of long-term monolayer cultures of human granulosa cells from follicles of different size and exposed in vivo to clomiphene citrate and hCG.

To determine the effects of prolonged hCG treatment in vitro upon granulosa cells from follicles of various sizes previously exposed to clomiphene citrate and hCG in vivo, progesterone and relaxin concentrations of spent media were correlated with light microscopic and ultrastructural characteristics. Intact, freshly dispersed cells were characterized by numerous lipid droplets, elliptical mitochondria with tubular or lamellar cristae, moderate rough-surfaced endoplasmic reticulum (RER), sparse smooth-surfaced endoplasmic reticulum (SER), and few Golgi. After 10-24 days in culture, 2 morphologically distinct cell types, 'granulosa-type' and 'luteal-type', were noted at the light microscopic level. Ultrastructurally, lipid droplets decreased in number, mitochondria became pleomorphic, RER became more prominent and dilated, and Golgi became more widely dispersed. Tubular SER became abundant and annular nexuses became more numerous after hCG treatment in vitro. Granulosa cells generated from all follicles responded to hCG treatment with significantly increased progesterone secretion after 4 days in culture. Relaxin was not detectable in any sample of medium. This study shows that human granulosa cells from 15-25-mm follicles retain their differentiated function of progesterone secretion in long-term culture and recover responsiveness to hCG in vitro, as demonstrated by enhanced progesterone secretion and development of prominent SER and increased annular nexuses.

Cells, Cultured↗
PubMed1994

Is treatment of long-term and consecutive use of clomiphene citrate effective in anovulatory patients? Results of multi-centric retrospective studies.

The efficacy of long term consecutive treatment of clomiphene citrate (CC) was investigated in 608 infertile women associated with anovulatory disorders (classified as WHO group II amenorrhea). This study was performed in multi-centric facilities of obstetrics and gynecology by a retrospective randomized assessment. Infertile women associated with anovulation were treated by 50-150 mg of CC for five consecutive days in each treatment cycle. In this study, 200 pregnancies were observed and the total pregnancy rate was 32.9%. The number of abortions were 33 out of the 200 pregnancies (16.5%). The cumulative pregnancy rate within the pregnant subjects reached 90% in initial 10 treatment cycles and there was no difference between 50 mg and 100 mg of CC treatment. There were remarkable differences among the pregnancy rates achieved during consecutive treatments at the primary (clinics and hospital), secondary (regional center hospitals) and advanced facilities. Consecutive treatment by CC for infertile women associated with anovulation may be effective during initial 10 cycles. Although ovulation can be confirmed during the following cycles, the stimulation protocol should be reconsidered after 12 consecutive cycles therapy with CC, because cycle fecundity decreases. Hence, to improve pregnancy rates, it is important to check the previous administration of CC which reflects adversely on the subsequent conception rate especially in advanced facilities where these patients are referred to.

Anovulation↗
PubMed1978

Concentrations of prostaglandins F2alpha and E2 in the endometrium throughout the human menstrual cycle, after the administration of clomiphene or an oestrogen-progestogen pill and in early pregnancy.

The concentrations of prostaglandins F2alpha (PGF) and E2 (PGE) were measured by gas chromatography-mass spectrometry in endometrial tissue obtained from 45 normal women at various stages of the menstrual cycle. During the proliferative stages, the concentration of PGF in the endometrium was correlated with the concentration of oestradiol in the plasma. The concentration of PGF during the mid-secretory stage (mean, 2.047, range, 0.549-4.344 microgram/g fresh endometrial tissue) was significantly higher than the concentrations during the late proliferative and late secretory stages. The endometrial concentration of PGE did not show a cyclic variation. The concentrations of PGF and PGE in samples of endometrium collected after the administration of clomiphene were significantly lower than the concentrations observed in endometrial tissue obtained from normally menstruating women in the mid-proliferative period. The administration of an oestrogen-progestogen pill resulted in higher endometrial concentrations of PGE than were measured in the mid-secretory phase. The concentrations of PGF and PGE in decidual tissue (conceptual age 3-10 weeks) were lower than those measured at any stage of the normal menstrual cycle. During the human menstrual cycle, high levels of oestradiol and progesterone are related to high endometrial levels of PGF but not PGE. The presence of a conceptus apparently blocks the effect of high concentrations of ovarian steroids on the synthesis or catabolism of prostaglandins.

Adolescent↗
PubMed1980

Clomiphene and tamoxifen action in the rat uterus.

The antioestrogens clomiphene and tamoxifen exhibit both agonistic and antagonistic properties in the rat uterus. The effect of these antioestrogens on RNA polymerase activities in the rat uterus was investigated. Both compounds stimulated an early increase in the activity of endogenous RNA polymerase B similar to that observed after oestradiol treatment. A secondary stimulation of activity of RNA polymerase B was observed after treatment with oestradiol and both antioestrogens. In addition, the activity of endogenous RNA polymerase A was increased initially at 1 h by all three compounds but this activity was maintained at 24 h only by oestradiol.

Animals↗
PubMed1980

Alterations induced by clomiphene in the concentrations of oestrogen receptors in the uterus, pituitary gland and hypothalamus of female rats.

Alterations in the concentrations of oestrogen receptors in the uterus, pituitary gland and hypothalamus during the 2 weeks following a single administration of clomiphene citrate (Clomid) to immature, bilaterally ovariectomized rats were investigated. Examination of the uterine wet weight at 1, 7 and 14 days following a single injection of Clomid (100 micrograms, 250 micrograms or 10 mg) indicated significant time- and dose-related increments from a control value of 45 +/- 2 (S.E.M.) mg to a maximum of 123 +/- 3 mg (250 micrograms dose at 14 days). In contrast, a single injection of oestradiol led to a transient increase in the uterine weight on day 1 to 94 +/- 6 mg, but was without effect by days 7 and 14. Analysis of the uterine DNA content 7 and 14 days after treatment with Clomid revealed significant increments from control values of 390 +/- 10 micrograms to a high level of 558 +/- 9 micrograms (10 mg dose at 7 days). There was a transient retention of nuclear oestrogen receptors and rapid replenishment of cytoplasmic oestrogen receptors in less than 24 h in the uteri of animals treated with oestradiol (25 micrograms), but determinations of receptor content in Clomid-treated animals revealed prolonged retention of nuclear receptors and delayed replenishment of cytoplasmic receptors. The duration and extent of retention of nuclear receptors and depletion of cytoplasmic receptors after treatment with Clomid were found to be dose-dependent. Fourteen days after Clomid treatment, levels of oestrogen receptors in nuclei from the uterus were still raised in all treatment groups, whereas replenishment of cytoplasmic receptors was complete in animals treated with the lower doses (100 and 250 micrograms) of Clomid. A single injection of Clomid (250 micrograms) induced similar prolonged retention of nuclear receptors and delayed depletion of cytoplasmic receptors in pituitary tissue. In contrast, changes in the content of oestrogen receptors in the hypothalamus following Clomid treatment were minimal. The limited effect of Clomid on hypothalamic tissue may mean that the pituitary gland is a more important target for this compound than is the hypothalamus. The findings have confirmed earlier reports on the long-term uterotrophic effect of Clomid and have suggested that under these long-term, in-vivo conditions, Clomid acts in the uterus and pituitary gland as a long-acting oestrogen characterized by prolonged retention of oestrogen receptors in the nucleus and delayed, but otherwise effective, replenishment of the oestrogen receptors in the cytoplasm.

Animals↗
PubMed1984

Effect of ovariectomy and clomiphene on the in-vitro incorporation of [3H]thymidine into pituitary DNA and on prolactin synthesis and release in rats.

In the anterior pituitary gland changes in prolactin synthesis and in the incorporation of [3H]thymidine into DNA are coincident under several experimental conditions. We investigated whether these changes are obligatory, thus indicating a regulatory mechanism common to the synthesis of both macromolecules. Alternatively, the parallel changes may represent similar responses to various stimuli operating through different pathways. The administration of alpha-methyl-p-tyrosine (alpha MpT) to rats stimulated the incorporation of [3H]leucine into prolactin and [3H]thymidine into DNA. When the effectiveness of oestrogen was suppressed by ovariectomy or by blockage of oestrogen receptors by the antioestrogen clomiphene, alpha MpT stimulated the synthesis of prolactin but not the incorporation of [3H]thymidine into pituitary DNA. The results clearly indicate two independent mechanisms regulating the synthesis of prolactin and DNA in the anterior pituitary gland.

Animals↗
PubMed1986

Influence of clomiphene citrate in vivo on subsequent steroid formation and gonadotropic responsiveness in vitro of isolated human follicular cells.

Granulosa and thecal cells from human preovulatory follicles, extirpated from the ovaries of women undergoing sterilization by minilaparotomy, were incubated for 2 hours in the presence or in the absence of human gonadotropin (hCG). The follicles were obtained from 16 women, 8 of whom had previously been treated with clomiphene citrate (CC) to induce follicular maturation. The tissue contents of cyclic AMP (cAMP) and the content of progesterone (P), testosterone (T) and estradiol-17 beta (E2) in the incubation medium were measured. Granulosa and thecal cells from control and CC-induced follicles all responded to hCG in vitro with increased formation of cAMP. Both granulosa and thecal cells from CC-induced follicles produced larger amounts of P in vitro than cells from spontaneously matured follicles. There were no other differences in the patterns of steroid formation or reactivity to hCG between the cells from the two types of follicle. It is concluded that CC treatment in vivo induces the growth and maturation of preovulatory follicles with apparently normal biochemical characteristics, as far as the content of and capacity to form cyclic AMP, progesterone, testosterone and estradiol-17 beta are concerned.

Adult↗