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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

Radioimmunoassays of ethinyl-norgestrienone (R-2323) and medroxyprogesterone acetate (MPA) and their clinical applicability.

Radioimmunoassays for 2 synthetic progestins (Ethinyl-norgestrienone, R 2323 and medroxyprogesterone acetate, MPA) are demonstrated. 10 patients aged 31 to 72 years were treated with ethinyl-norgestrienone with different schedules and 3 men suffering from benign prostatic hypertrophy were treated with medroxygesterone acetate. Plasma levels of testosterone, LH, FSH were monitored before, during and after treatment.

Adult

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

Effects of aging on the hypothalamic-hypophyseal-gonadal axis in female rats.

The failure of reproductive function in aged rats could be due to deficiencies at the level of the ovary, pituitary, hypothalamus, or higher brain centers. The classic explanation that the ovary is depleted of follicles does not receive adequate support on the basis of histologic studies of aged ovaries. Basal serum gonadotropin levels change with increasing age in female rats. Serum follicle-stimulating hormone (FSH) levels rise while serum luteinizing hormone (LH) levels fall. Likewise, the characteristic response to castration is markedly altered in aged female rats with a reduced secretion of FSH and a minimal elevation of LH. However, the pituitaires of these animals are still caapable of responding to exogenous LH-releasing hormone with a delayed LH response whose magnitude simulates that seen in younger female animals. With increasing age there is decreased pituitary and/or hypothalamic sensitivity to the feedback action of estradiol. These data are consistent with the postulation that there is an altered hypothalamic-hypophyseal function in aged rats.

Aging

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

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

Restoration of the gonadotrophin response to LH-RH and oestrogen administration in patients after molar abortion.

The relation of the hypothalamic-pituitary effect on gonadotrophin secretion and the concentration of serum hCG after molar abortion was investigated. Gonadotrophin release after a bolus injection of LH-RH or conjugated oestrogens was observed in 17 women until 5 months after molar abortion. Little if any response of gonadotrophin was observed at a hCG level of 100 mIU/ml or more, but the response of LH and FSH to LH-RH were restored to normal when the serum hCG level decreased to below 100 mIU/ml. A normal response of LH to conjugated oestrogens was observed at a serum hCG level of 20 mIU/ml or less. These findings suggest that a high level of hCG interferes with pituitary gonadotrophin secretion, that the threshold hCG levels for normal responses of gonadotrophins to LH-RH and oestrogen are 100 and 20 mIU/ml, respectively, and that secretion of gonadotrophins is restored even in the presence of a low hCG level.

Adult

Binding of LH and FSH to porcine granulosa cells during follicular maturation.

The uptake of 125I-labelled LH by equal numbers of granulosa cells from small, medium or large follicles was greater by cells from large follicles. In contrast, granulosa cells obtained from small follicles bound much more 125I-labelled FSH per cell than did cells obtained from medium and large follicles. Competition studies with unlabelled hormones indicated that porcine granulosa cells have specific receptors for LH and FSH. The addition of diethylstilboestrol enhanced the binding of 125I-labelled LH and inhibited the binding of 125I-labelled FSH to granulosa cells harvested from small and medium-sized follicles, but had no effect on those from large follicles.

Animals

Steroid sex hormones and prolactin in postmenopausal women with generalized mammary carcinoma during prolonged dexamethasone treatment.

The endocrine response to prolonged dexamethasone treatment was investigated in six postmenopausal women with generalized mammary carcinoma. Plasma cortisol levels decreased rapidly and became undetectable whereas significant concentrations of plasma dehydroepiandrosterone and androstenedione persisted throughout the study, even in two ovariectomized patients, indicating a certain degree of autonomy or a greater resistance of adrenal 'androgens' to the inhibition of ACTH secretion. Except in the ovariectomized patients, plasma testosterone did not fall significantly whereas the plasma oestrogens tended progressively towards undetectable concentrations. A similar response was found in six normal postmenopausal women although the disappearance of their oestrogens was relatively rapid. This indicates that much of the testosterone present after the menopause could still be produced by the ovaries whereas the ovarian production of oestrogens becomes negligible. The delayed disappearance of oestrogens in the patients with mammary carcinoma indicates that the persisting adrenal 'androgens' remained efficient precursors of oestrogen synthesis within the peripheral tissues and presumably within the mammary tumour itself. Plasma dihydrotestosterone behaved like the plasma oestrogens. Despite the fall in plasma oestrogens, plasma gonadotrophins did not increase further but plasma prolactin rose progressively. The persistance of steroid sex hormones and the rise of plasma prolactin might explain the poor response to dexamethasone treatment in mammary carcinoma.

Aged

Premature ovarian failure.

Twelve cases of premature ovarian failure (POF) are described. The clinical, hormonal, histopathologic and cytogenetic studies of each patient have been presented. The scope and the limitations of laparoscopic ovarian biopsy are discussed, as is the importance of radioimmunoassay of follicle-stimulating and luteinizing hormones (FSH/LH) in comparison to ovarian biopsy for the diagnosis of premature ovarian failure. A plea is made for the early diagnosis of POF so that these young women can be spared the expensive and time-consuming treatment for the associated problem of infertility.

Adult