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PubMed1975

Clinics in endocrinology and metabolism. Investigative procedures.

In patients with hypogonadism, the exact cause of the deficient androgenisation is not always clinically apparent. The data presented demonstrate that by means of hormone measurements, basally or after stimulation tests, the exact level of the lesion can usually be determined. This allows a decision with regard to appropriate therapy to be made on the basis of an accurate diagnosis. In many instances basal measurements of pituitary and gonadal hormones are all that is required to decide the level of the lesion. Care in interpreting basal levels is required, however, in view of methodological limitations and of known physiological variations with age, time of day and hour-to-hour fluctuations. If the basal hormone levels are borderline, or if the 'reserve function' of part or all of the hypothalamic-pituitary-gonadal axis needs to be assessed, than the appropriate stimulation test should be performed. The indication for these stimulation procedures and results obtained in different conditions are described and problems of interpretation discussed.

Adult↗
PubMed1977

A syndrome of functional hypogonadotropic hypogonadism and sterility in a male with elevated serum estradiol.

A 36-year-old male complaining of impotence was examined. He was a genotypic male. Phenotypically, he exhibited signs of long-standing estrogen excess, such as feminine body build, gynecomastia, and varicose veins. His testes were soft and borderline small, and his prostate was small and soft. However, he had a normal-sized penis, normal male hair distribution, normal sense of smell, and normal intelligence. The laboratory data were compatible with mild hypogonadotropic hypogonadism. Serum estradiol (E2) levels were consistently elevated. The patient had azoospermia and a decreased semen volume. Inappropriately low levels of luteinizing hormone and follicle-stimulating hormone responded normally to gonadotropin-releasing hormone and clomiphene citrate. Levels of both testosterone (T) and E2 increased dramatically after prolonged clomiphene medication and in response to human chorionic gonadotropin. There was no change in either T or E2 levels in response to manipulations of the pituitary-adrenal axis. It is concluded that the elevated E2 level was responsible for suppression of gonadotropins which, in turn, caused mild hypogonadism and sterility in this patient. According to the stimulation tests, the source of the elevated E2 levels was testicular.

Adolescent↗
PubMed1975

On the regulation of fetal and maternal 16 alpha- hydroxydehydroepiandrosterone and its sulfate by cortisol and ACTH in human pregnancy at term.

In studying the mechanisms which govern estriol production in human pregnancy at term, 16 alpha OH-DHEA, 16alpha-OH-DHEA sulfate, and unbound unconjugated cortisol were measured in peripheral venous plasma of 28 healthy women and in cord venous and arterial plasms of their newborn infants at the time of elective cesarean section prior to the onset of labor. In eight cases treated with 150 mg. of cortisol, maternal and cord plasma 16alpha-OH-DHEA and its sulfate were considerably lower than in 10 control cases. Approximately 4 to 8 1/2 hours after injection of 40 I.U. of Depot-ACTH, both of these estriol precursors were also significantly decreased. It is concluded from these experiments that cortisol causes a decrease of estriol mainly by suppressing fetal 16alpha-OH-DS.

Adrenocorticotropic Hormone↗
PubMed1977

Immunoglobulins, proteinase inhibitors, albumin, and lysozyme in human cervical mucus. I. Communication: hormonal profiles and cervical mucus changes--methods and results.

The serum levels of luteinizing hormone (LH), estradiol-17beta, and progesterone were determined simultaneously with the concentrations of immunoglobulin (Ig) G, IgA, C'3, alpha1-antitrypsin, inter-alpha-trypsin inhibitor, alpha1x-antichymotrypsin, albumin, and lysozyme in cervical mucus during nine ovulatory cycles. Spinnbarkeit and ferning were also assessed, and the basal body temperature was measured and recorded during these cycles. The profiles were synchronized according to the LH peak. The midcycle period, characterized by the rapid increase and decline of estrogen and the beginning rise of progesterone, shows a prounced minimum of immunoglobulins, C'3, proteinase inhibitors, albumin, and lysozyme in cervical mucus, which is known to be most receptive to sperm penetration at this time. Although the variation of cervical mucus values is considerable during the early proliferative and the luteal phases, the midcycle values appear to be constantly low, showing slight differences among the profiles of the different parameters. The statistical evaluation and the assessment of the significance of parameters for ovulation detection and the assessment of the fertile period as well as the correlation of these parameters with basal body temperature will be the subject of the second communication of this series.

Adult↗
PubMed1978

The effect of oral contraceptive treatment on the serum concentration of dehydroisoandrosterone sulfate.

Dehydroisoandrosterone sulfate (DS), the major C19-steroid in the human circulation, was measured in serum obtained from blood samples collected daily (8 to 10 A.M.) throughout the menstrual cycles of eight normal, presumably ovulatory women and daily throughout the treatment cycles in four women taking an oral contraceptive (norethindrone, 1 mg., plus mestranol, 80 mcg.). The serum concentrations of DS in the ovulatory women ranged from 1,025 to 4,200 ng. per milliliter; mean, 2,062 +/- 137 ng. per milliliter (mean and standard error; n = 213). Serum DS concentrations during the follicular and luteal phases of the menstrual cycles of these women were similar. In women taking the oral contraceptive, the plasma DS concentrations ranged from 475 to 1,400 ng. per milliliter (mean, 895 +/- 83; n = 119). The 24 hour secretory pattern of DS was evaluated in one subject during a nontreatment cycle and again after 20 days of oral contraceptive treatment. In this subject, the mean serum DS level was 34 per cent lower during oral contraceptive treatment than the level before treatment. The decrease in the serum concentration of DS during oral contraceptive treatment likely results from a reduction in adrenal DS secretion since DS secretion by the normal human ovary is negligible and ovarian dehydroisoandrosterone secretion is small. Therefore, it is likely that the reduced serum DS levels in women taking oral contraceptives are the consequence of reduced adrenal secretion of DS resulting from reduced release of adrenocorticotropic hormone.

Adrenal Cortex↗
PubMed1977

Recovery of preimplantation blastocysts in the squirrel monkey by a laparoscopic technique.

A laparoscopic uterine flushing technique has been developed for the recovery of preimplantation embryos from the squirrel monkey. Fourteen adult female squirrel monkeys were induced to ovulate with 4 or 5 days' treatment with follicle-stimulating hormone (1 mg) followed by human chorionic gonadotropin (HCG) (500 IU). Natural mating with a fertile male or artificial insemination was performed near the time of ovulation. Thirty-six hours and eleven days after HCG administration, the females were laparoscoped to determine whether ovulation had occurred. Under laparoscopic control, 1.2 to 3 ml of warmed saline were flushed through the uterine lumen 4 to 7 and 15 to 17 days after HCG administration. Flushed fluid was recovered with a plyethylene catheter or a Pasteur pipette inserted into the cleaned vagina. Fifty-eight uterine flushings were performed, with an average of 65.4% fluid recovery. Six nonfertilized ova and two preimplantation blastocysts were recovered by this technique.

Animals↗
PubMed1979

Adrenal steroids and the development of osteoporosis in oophorectomised women.

To explore the possibility that the wide variation in bone loss among oophorectomised women might be due to differences in adrenal androgens or their biosynthetic pathways, 18 women (10 with very fast and 8 with very slow bone loss) were selected. Serum levels of nine adrenal steroids, including the major androgens and cortisol, were measured under basal conditions and after overnight suppression followed by acute corticotropin stimulation. In addition, basal serum oestrone, oestradiol, dehydroepiandrosterone sulphate, sex-hormone-binding-globulin, corticosteroid binding globulin, and urinary free cortisol were measured. The only significant differences found were that women who lost bone rapidly had significantly higher urinary free-cortisol excretion (p less than 0.001) and a paradoxically diminished cortisol response to corticotropin. These data make it unlikely that endogenous adrenal androgens or oestrogens are a major factor in preventing bone loss after cessation of ovarian function; cortisol by its catabolic effect, however, may be a significant factor in causing osteoporosis.

17-Ketosteroids↗
PubMed1975

Guanidination of ovine luteinizing hormone and effects on activity.

The free amino groups in oLH, oLHalpha and oLHbeta were guanidinated by O-methylisourea. The epsilon-NH2 groups of lysine residues reacted bo substitute these positions in the sequence with the more basic homoarginine residue. The alpha-NH2 groups did not react under the conditions used. Guanidinated oLH or the products of guanidinated oLHalpha + native oLHbeta or guanidinated oLHalpha + guanidinated oLHbeta were inactive in two bioassay systems. Native oLHalpha + guanidinated oLHbeta, however, showed potencies of 39% to 55% of that observed with the native subunit recombinant or native oLH. Possible structural implications for hormone-receptor site interactions are discussed.

Amino Acids↗
PubMed2026

Evaluation of metabolic, reproductive, and gut microbiota alterations in a comparative study of different preclinical models of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a multifaceted, complex metabolic and endocrine disease where gut flora is considered an important factor in causing PCOS. This study aimed to identify a suitable PCOS model that contributes to gut microbial dysbiosis and metabolic and hormonal disturbances. Prepubertal SD rats were administered with normal control (NC), dihydrotestosterone (DHT), DHT with fructose (F), DHT+ high fat diet (HFD) for 91 days, dehydroepiandrosterone (DHEA), DHEA with fructose, DHEA with HFD for 30 days, sodium valproate (SV), sodium valproate with fructose, and sodium valproate with HFD for 21 days. The estrous cycles were assessed over this timeframe. At the end of the experiment, superoxide dismutase and uterine and ovarian morphology were evaluated, along with hormone levels, lipid profiles, and 16S rRNA genomic sequencing. All models exhibited PCOS characteristics, including hormonal imbalances, insulin resistance (p ≤ .001), multiple follicular cysts on ultrasonography, and histological alterations. Gut microbial dysbiosis was observed across all PCOS-induced groups; however, the DHT alone group showed more pronounced alterations in microbial composition than the other experimental groups. Specifically, the DHT alone group exhibited reduced abundance of Firmicutes and increased abundance of Proteobacteria. Among the evaluated models, the DHT-only model showed more pronounced metabolic, hormonal, reproductive, and gut microbial alterations and may serve as a suitable model for PCOS research.

Animals↗
PubMed1978

Detection of ovulation by a radioreceptor assay for human luteinizing hormone.

A specific, sensitive, and rapid radioreceptor assay (RRA), employing membranes from bovine testes as receptor and [125I]hLH as radioligand, has been developed for measurement of human LH in serum. This RRA was used to determine the time of ovulation in seven women. For comparison, four hourly values around midcycle were measured by RIA. The sensitivity of the RRA was 0.78 ng/ml serum and could be increased by prolonged incubation. The coefficient of within and between assay variation at the 50% inhibition level was 7% and 13%, respectively. The mean index of discrimination (RRA/RIA) was 1.02, expressed by the slope of the regression curve. The coefficient of correlation was 0.97. In all women, the LH surge was detected by RRA, and the subsequent ovulation was verified within 30 h by endoscopic examination of the ovaries, as well as serum progesterone concentrations of more than 5 ng/ml on the fifth day after ovulation. As shown, prospective ovulation timing can be done by this simple and accurate method. The RRA can be useful in infertility therapy such as artificial insemination.

Adult↗
PubMed1978

The relationship of changes in serum estradiol and progesterone during the menstrual cycle to the thyrotropin and prolactin responses to thyrotropin-releasing hormone.

The responses of serum TSH and PRL to TRH (500 microgram) were studied in normal young women in the early follicular, periovulatory, and midluteal phases of the menstrual cycle in order to examine the relationship of these responses to the levels of estradiol relationship of these responses to the levels of estradiol (E2) and progesterone. Each woman was studied twice in each phase in order to assess intraindividual variability. There was no significant difference in either the TSH or PRL responses among the phases of the menstrual cycle nor was either response affected by the periovulatory rise in E2 or by the luteal rise in both E2 and progesterone. Thus, the interpretation of the TSH and PRL responses to TRH in normal women is not affected by the menstrual cycle although both responses are greater in women that in men. Both the peak TSH and peak PRL after TRH were highly correlated with the basal levels of TSH (r = 0.85; P less than 0.01) and PRL (r = 0.67; P less than 0.01), respectively, indicating that the TSH and PRL responses to TRH in women are directly proportionate to the basal levels of the respective hormones, as previously shown for the TSH response in men. The mean intraindividual variability (coefficient of variation) of the TSH response to TRH was 18%, but ranged as high as 56%, while that of the PRL response was 16% and ranged up to 31%; variability was not affected by the phase of the menstrual cycle. The normal range of the peak TSH after TRH in women is 7-33 microU/ml (mean +/- 2 SD); however, because of the variability, a normal woman may sometimes have a peak TSH after TRH as low as 4 microU/ml. Repeating the test will result in a normal value if the woman is truly normal. Similarly, the normal peak PRL after TRH in women is 22-111 ng/ml (mean +/- 2 SD); usually, however, the lower limit is 30 ng/ml with lower values due to intraindividual variation. The data suggest that the higher average level of E2 in women compared to women, but that the cyclic changes in serum E2 or progesterone in women have little or no additional effect.

Adult↗
PubMed1979

Effect of oral contraceptive containing a new progestin (ORG 2969) on plasma renin activity, growth hormone and immunoreactive insulin.

Plasma renin activity (PRA), Growth hormone (GH) and immunoreactive insulin (IRI) were studied in seven healthy subjects during the ovulatory menstrual cycle and during the first and third cycles of oral contraception with 0.05 mg of ethinylestradiol and 0.100 mg or 0.125 mg of a new progestogen, 17 alpha-ethinyl-18-methylene-4-estren-17 beta-ol. The PRA level in the second half of the control cycle was significantly higher than in the beginning of the cycle. At the end of the treated cycles it was significantly higher than at the end of the control cycle. Neither GH nor IRI showed significant changes during the control cycle. GH was significantly higher at the end of the first and third treated cycles than at the end of the control cycle. IRI was significantly higher both in the beginning and at the end of the first treated cycle than the corresponding IRI levels in the control cycle. IRI at the end of the third treatment cycle was not significantly different from corresponding means at the end of the control cycle or the first treated cycle.

Adult↗