Biological and Phytochemical Screening of Plants

Biological aromatization of steroids

To evaluate gonadotropin release in polycystic ovary syndrome (PCO), one or more of the following hypothalamic-pituitary function tests were performed on 24 patients with the syndrome. These tests included (a) the pulsatile pattern and day-to-day fluctuation of gonadotropin release; (b) effects of exogenous estrogen and antiestrogen (clomiphene) administration on gonadotropin release; and (c) pituitary responsiveness to maximal (150 mug) and submaximal (10 mug) luteinizing hormone-releasing factor (LRF) injections. In 10 of the 14 patients sampled frequently (15 min) for 6 h, luteinizing hormone (LH) levels were elevated above the concentration seen in normal cycling women (except the LH surge). These high LH concentrations appeared to be maintained by and temporally related to the presence of exaggerated pulsatile LH release, either in the form of enhanced amplitude or increased frequency. In all subjects, levels of follicle-stimulating hormone (FSH) were low or low normal, and a pulsatile pattern was not discernible. In four patients, daily sampling revealed marked day-to-day fluctuation of LH but not FSH. That the elevated LH levels were not related to a defect in the negative-feedback effect of estrogen was suggested by the appropriate fall of LH in four patients given an acute intravenous infusion of 17beta-estradiol. This infusion had no effect on FSH levels. In addition, clomiphene elicited rises of both LH and FSH that were comparable to the ones observed in normal women given the same treatment. The clomiphene study also suggested that the positive-feed-back mechanism of estrogen on LH release was intact when the preovulatory rises of 17beta-estradiol induced appropriate LH surges. The elevated LH levels appeared to be related to a heightened pituitary responsiveness to the LRF. This was found in the 11 and 2 patients given maximal (150 mug) and submaximal (10 mug) doses of LRF, respectively. The augmented pituitary sensitivity for LH release correlated with the basal levels of both estrone (P less than 0.025) and 17beta-estradiol (P less than 0.02). The net increase in FSH was significantly greater (P less than 0.001) in the PCO patients than the normal women with maximal doses of LRF. With the smaller dose study none of the injections had a discernible effect on FSH concentrations in either subject. The disparity between LH and FSH secretion could be explained by the preferential inhibitory action of estrogen on FSH release, coupled with a relative insensitivity of FSH release. These data indicate that in these PCO patients the abnormalities of the hypothalamic-pituitary regulation of gonadotropin secretion was not an inherent defect but represented a functional derangement consequent to inappropriate estrogen feedback, which led to a vicious cycle of chronic anovulation and inappropriate gonadotropin secretion.

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Characterization of the inappropriate gonadotropin secretion in polycystic ovary syndrome.

Continuous infusions of Delta(4)-androstenedione-7-(3)H and testosterone-7-(3)H have been used to demonstrate that these androgens are converted to estrone and 17beta-estradiol, and contribute to the circulating blood levels of these estrogens in normal males and females. The conversion ratio (ratio of concentrations of radioactivity of free product steroid [chi(-PRO)] and free precursor steroid [chi(-PRE)], both corrected for recoveries, after an infusion of radioactive precursor steroid) for androstenedione (precursor) to estrone (product) is 0.013 in males and 0.007 in females, and the conversion ratio for testosterone (precursor) to estradiol (product) is 0.0018 in males and 0.005 in females. The transfer constant, [rho](BB) (AE1), for androstenedione conversion to estrone ([rho](BB) (AE1) = per cent of infused androstenedione, precursor, converted to estrone, product, when infusion and measurement are both in blood) is 1.35% in males and 0.74% in females, and the transfer constant, [rho](BB) (TE2), for testosterone conversion to estradiol is 0.39% in males and 0.15% in females. Whether measured as conversion ratio or transfer constant, the peripheral aromatization of androstenedione takes place to a greater degree than that of testosterone, and, for the respective androgens, both the conversion ratio and [rho](BB) value are greater in males than females. For the androgen interconversions, [rho](BB) (AT) is 4.5% in males and 2.2% in females; [rho](BB) (TA) is 8.2% in males and 12.0% in females. Studies on the distribution coefficients (effective concentration in red cells/plasma) for precursor radioactivity were also made. In both males and females the distribution coefficient for androstenedione is 0.16-0.17 while that of testosterone is 0.01-0.03.

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Conversion of blood androgens to estrogens in normal adult men and women

A dehydration procedure has been used to identify patients with partial antidiuretic hormone (ADH) deficiency. The test consists of water deprivation until the osmolality of hourly voided ...

Recognition of partial defects in antidiuretic hormone secretion.

Certain alterations in endocrine balance have been shown to constitute effective palliative therapy for some patients with breast cancer. Surgical castration, adrenalectomy, administration of estrogens, and administration of androgens have been demonstrated to produce objective remissions in some patients, whereas in other patients the treatment is without effect or may actually accelerate the growth of the neoplasm. Weeks or months of clinical observation are usually required following a given therapeutic procedure to determine whether the desired effect is being obtained. An objective index of alterations in tumor growth in man would provide an invaluable guide to the selection of the proper therapy for the individual patient with breast carcinoma. Such an objective measurement is afforded by determining the rate of bone destruction in patients with osseous metastases that are predominantly osteolytic in type. Since bones are a favorite site for metastases from breast carcinoma, calcium excretion studies provide a practical,

Evaluation of endocrine therapy for advanced breast cancer.

Conversion of testosterone to estrogens in castrated, adrenalectomized human females.

Diabetes insipidus has been the subject of extensive animal investigations during the last twenty-five years, but the clinical counterparts of these studies have been few. This is due, not only to the rarity of the disease and its variable pathology, but also the considerable difficulty attending the diagnosis in its milder forms. We have had a unique opportunity to observe the delveolpment of diabets insipidus in several patients who have undergone hypophysectomy for metastatic cancer. We shall discuss the alterations in water exchange following surgery, and some of their physiologic implications.

An analysis of the polyuria induced by hypophysectomy in man.

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Adrenocortical hyperfunction in "idiopathic" hirsutism and the stein-leventhal syndrome'

A varying degree of hypertrichosis is a common clinical finding in adult females (1). When hair growth is slight there may be only a cosmetic problem; when profuse, the effect may be psychologically debilitating (2) and indicative of a deep seated endocrine abnormality. A small number of women with this condition may, upon extensive clinical examination, exhibit one of a variety of endocrine disorders arising from hyperplastic or neoplastic changes in the pituitary, adrenals or ovaries (2, 3). The majority, however, for want of evidence of specific endocrine disease, fall into a group referred to as “idiopathic” or, if the history warrants, “familial” hirsutism.

Charles D. West

Papers

Evaluation of endocrine therapy for advanced breast cancer.

Conversion of testosterone to estrogens in castrated, adrenalectomized human females.

An analysis of the polyuria induced by hypophysectomy in man.

Adrenocortical hyperfunction in "idiopathic" hirsutism and the stein-leventhal syndrome'

A study of "idiopathic" hirsutism; a transitional adrenal abnormality.