Gonadotropin-gonadal interrelationships in the fetus.
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Biomedical subjects
Publications and source records attributed to C Faiman.
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Concentrations of human chorionic gonadotropin (HCG) and progesterone were measured in the peripheral sera of 101 normal pregnant women between 25 and 41 weeks' gestation. HCG levels rose significantly with advancing gestation in the 43 female-bearers (r equals 0.516, p less than 0.001), whereas the 58 male-bearers showed no change (r equals 0.168, p greater than 0.1). Mean HCG levels were significantly higher in female- than in male-bearers (10.7 plus or minus standard error 1.0 versus 8.0 plus or minus 0.9 International Units per milliliter; p less than 0.05). Progesterone levels rose significantly in both female- and male-bearers. The calculated regression lines and mean levels (female-bearers 9.1 plus or minus 0.5; male-bearers 9.8 plus or minus 0.4 mug per deciliter) were not significantly different. There was no correlation between HCG and progesterone levels in either sex or in the entire group independent of gestational age. It is postulated that the lower HCG levels observed at term in male-bearers may result from an inhibitory influence of the higher progesterone and/or androgen concentrations in the male umbilical arterial circulation.
Serum levels of FSH, LH, chorionic gonadotropin (CG), prolactin, estrone (E1), estradiol-17Beta (E2), estriol (E3) and progesterone were measured at 2-3-day intervals in 4 chimpanzees through 2-3 menstrual cycles, and serially through subsequent pregnancies. The hormone patterns of the menstrual cycles were similar to those in man, with high levels of FSH in the early follicular phase, followed by rising E2 concentrations to a peak (up to 35 ng/dl) at or just before a midcycle LH/FSH peak. In most cycles there was a secondary E2 rise and progesterone rose to values above 500 ng/dl during the luteal phase. There was no consistent pattern in prolactine levels through 3 menstrual cycles. A simultaneous increase in E2 and LH/CG levels and a fall in FSH about 10 days postovulation indicated fertilization and implantation. Other early signs of pregnancy were persistent luteal range progesterone concentrations and rising levels of E1 and E3. Peak CG levels (56-154 IU/ml) occurred 30-50 days after the midcycle LH/FSH peak, followed by a decline and then a small secondary rise to (to 1 IU/ml) before term. E1, E2 and E3 levels rose more rapidly after 80 days to a peak at term (E1: 180-300 ng/dl; E2: 500-800 ng/dl; and E3:400-1000 ng/dl). Progesterone levels showed one peak coincident with the CG peak, and a secondary rise after about 80 days to maximal values at term of 49-120 ng/ml. Prolactin levels increased during pregnancy with irregular fluctuations (7-127 ng/ml). These findings indicate in contrast to observations in rhesus monkeys and baboons, that the hormonal patterns during pregnancy in the chimpanzee are remarkably similar to those in man. Thus, the chimpanzee should prove to be an ideal model for research directly applicable to human reproduction.
Mixed cord sera (27 male, 28 female) and sera from 105 male and 93 female children aged 5 days to 4 yr were assayed for FSH, LH and hCG. Cord hCG was similar in both sexes (median 58 mIU/ml; range 20-9000), and fell to less than 5 mIU/ml by 5 days of life, a value which is below the limit of detectable cross reactivity in the LH radioimmunoassay. Cord FSH was less than 5.5 mug LER-907/100 ml in both sexes. In boys there was a rapid rise of FSH in early postnatal life, with peak levels up to 55 mug/100 ml between 1 week and 3 months, followed by a decline by 4 months reaching the low values seen in older prepubertal subjects. This postnatal FSH rise was both more marked in females with peak values at 2-3 months up to 169 mug/100 ml, and also more sustained with levels staying above those of older prepubertal children until 4 yr of age. Serum LH levels in the boys were in the adolescent range by 1 week of age, peaked at 1 month and then declined to the usual childhood range by 4 months. A similar pattern, though with lower peak LH values, was seen in the female infants. A longitudinal study of serum FSH and LH values in one male and one female chimpanzee from 17 to 456 days of age showed patterns in serum gonadotropins which paralleled those seen in the human cross-sectional study.
Heterologous double-antibody radioimmunoassay methods are described for the measurement of circulating levels of rhesus monkey (Macaca mulatta) FSH and LH; the latter assay is also applicable to rhesus chorionic gonadotropin (CG) estimations. The FSH assay utilizes purified rat FSH for trace, either of two anti-human FSH antisera and a semipurified rhesus pituitary standard. The LH assay utilizes purified ovine LH for trace, an anti-human CG antiserum and the same rhesus pituitary standard. The use of these systems obviates the necessity of purifying rhesus gonadotropins which are required for the development of homologous radioimmunoassay systems.
A radioimmunoassay for rhesus monkey chorionic gonadotropin (mCG) employing an antiovine LH antiserum, 125I or 131I-ovine LH tracer, and mCG for standards was developed. Radioimmunoassay of serum levels of mCG during pregnancy indicated that mCG began increasing as early as day 12 after mating, reached a peak by day 25, and declined to nondetectable levels around day 35. The assay procedure was adapted for use as a rapid method for pregnancy diagnosis; the results were available as early as 12 hours after collection of serum samples. The method is capable of detecting a few pregnancies by day 12 and all pregnancies by day 17. Routine use of this method provided accurate pregnancy diagnosis four days earlier than was possible with the mouse uterine weight bioassay method previously used in this laboratory.
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Serum determinations of follicle-stimulating hormone and luteinizing hormone have been carried out in 13 prepubertal and adult patients who had been treated with courses of either oral or intravenous cyclophosphamide. All results were within the normal range for the patients' ages and sexual development. Although these results establish that gonadal endocrine function and pituitary-gonadal feedback relations may not be destroyed by cyclophosphamide, the possibility remains that prolonged cyclophosphamide therapy in young patients will result in some impairment of future fertility.
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Enlargement of an atrophic testis occurred in an oligospermic patient during long-term therapy with a low dosage of cisclomiphene. Orchidectomy revealed an adult teratoma combined with an atypical seminoma. The development of a germinal-cell neoplasm during pituitary-gonadal stimulation therapy raises the question of a possible cause-effect relationship. Available evidence does not support this possibility. However, it is less clear whether hormonal influences may promote the growth of a germ-cell tumour focus. Therefore, prolonged treatment with such agents demands close supervision, particularly in patients with a predisposition to gonadal carcinogenesis.
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