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Biomedical subjects

C HUGGINS

Publications and source records attributed to C HUGGINS.

At least 55 records · Page 3Linked to original sources
PubMed1955

The depression of estrone-induced uterine growth by phenolic estrogens with oxygenated functions at positions 6 or 16: the impeded estrogens.

Two small groups of steroids in the estrane series-here designated as impeded estrogens,-represent a class of compounds which differ from the majority of estrogenic substances in exerting certain unusual influences on growth of the uterus. The induction of these effects previously was considered to be peculiar to estriol. The unusual growth properties common to impeded estrogens are twofold: (a) after the threshold dosage required to initiate growth has been reached, the slope of the curve of increment of uterine weight in response to increased steroid dosage is very gradual rather than steep; (b) these compounds possess the ability to inhibit to a limited extent the uterine growth induced by estrone administered concurrently. The partial inhibition of estrone-induced growth of the uterus is confined to a critical dosage of the impeded estrogen and is overcome by increased dosage of the inhibitor. Estrone-induced growth of the vagina is not inhibited by impeded estrogens. Furthermore the simultaneous administration of impeded estrogens and testosterone does not lessen the amount of uterine growth evoked by the latter. The impeded estrogens so far encountered are 3-hydroxyestratriene derivatives possessing either a ketone group at position 6 or a hydroxyl group at position 16. Oxygenated functions at these positions in phenolic estrogens have special significance in the excitation and restraint of uterine growth unshared by similar groups at certain other sites of the estrane molecule.

Estrogens↗
PubMed1955

The depression of growth of the uterus, adrenals, and ovaries by fluorinated steroids in the pregnane series.

Progesterone, 5-pregnene-3,20-dione, and desoxycorticosterone were found to be partial but significant inhibitors of estrone-induced growth of the uterus of hypophysectomized rats but they did not depress the amount of growth elicited by testosterone. The presence of both the 2-carbon side chain at position 17 and an oxygenated function at position 3 is necessary for the inhibitory activity of progesterone. The introduction of a hydroxyl group in the progesterone molecule at positions 6 (beta), 11 (alpha), 16 (alpha) or 17 (alpha) destroyed its growth-inhibitory activity. 11beta-Hydroxyprogesterone is weaker than progesterone in the inhibition of estrone-induced uterine growth; unlike progesterone it has the capacity to depress growth elicited by testosterone. The introduction of a flourine atom in the 9 (alpha) position resulted in a striking increase of the growth-inhibitory activity of 11beta-hydroxyprogesterone and hydrocortisone. 9alpha-Flouro-11beta-hydroxyprogesterone is a partial but significant inhibitor of growth of the uterus in hypophysectomized rats injected simultaneously with large doses of estrone or testosterone. It is more powerful than progesterone in transforming the vaginal epithelium to mucus cells in the presence of estrone. Administered alone, the only detectable growth was a slight increase in size of the preputial glands. 9alpha-Flouro-11beta-hydroxyprogesterone suppresses in part the growth of the adrenals, ovaries, and uterus in intact rats at a dose level which does not cause loss of body weight or inhibit body growth. Many rats treated with this compound in small amount had extensive mucification of the vagina resembling that of late pregnancy.

Adrenal Cortex↗
PubMed1954

Chemical structure of steroids in relation to promotion of growth of the vagina and uterus of the hypophysectomized rat.

In the hypophysectomized albino rat which is protected from contact with steroids in the ration and environment the uterus and vagina are highly atrophic but are sensitive indicators of activity of substances which promote their growth. Both the pituitary growth hormone and certain steroids have the common property of inducing growth of these tissues. The vaginal epithelium consists of 2 layers of cells which differ profoundly in their growth in response to steroids, depending on the molecular structure of these compounds. The differential response to modifications of chemical structures of steroids permits evaluation of the importance of the intramolecular components for the process of growth. The number and site of functional groups, the geometry of the molecule and the state of oxidation are of high importance in determining physiologic activity of steroids in the androstane series; these features are less specific in the estrane series. Side groups at positions C(3) and C(17) are of importance in the promotion of growth by steroids in the androstane series, but these active centers are not equivalent in their physiological influence. As a generalization, hydrogenation of the oxygen function at C(17) (but not at C(3)) and dehydrogenation at critical areas of the ring structure increase the quantitative efficacy of steroids in promoting growth. The position of double bonds and the state of oxidation at both C(3) and C(17) determine the qualitative type of growth-cellular pattern, which a compound in the androstane series induces in the vaginal epithelium.

Animals↗
PubMed1954

Significance of the hydroxyl groups of steroids in promoting growth.

The presence of a 17beta-hydroxyl group endows the simple androstane molecule with the ability to produce growth of the uterus, vagina, and prostate of the female hypophysectomized albino rat. It appears that hydrogen atoms at position 17 are of critical importance since related compounds with a ketone group at this site are inactive. Monofunctional steroids with a hydroxyl or a ketone group at position 3 likewise are devoid of activity. If a phenolic A-ring is present in monofunctional steroids the 17beta-hydroxyl group is not obligatory for growth. Proliferation of the uterus and vagina were found to follow the administration of 17-desoxyestradiol.

Androstanes↗
PubMed1953

Quantitative studies of prostatic secretion. III. Simultaneous measurement of size and secretion of the canine prostate and the interaction of androgenic and estrogenic substances thereon.

The prostate of the dog was relocated permanently in the perineum where its size could be measured and correlated with the output of prostatic secretion during many months. The secretion of a submaxillary gland obtained through a fistula was utilized as an internal biologic standard of the effects of pilocarpine, the secretory stimulus employed, because the amount and route of administration of the alkaloid are critical factors in inducing secretion. Prostatic secretion was found to be profoundly affected by androgenic and estrogenic compounds, in contrast to salivation. The curves of the secretory response of the prostate and submaxillary glands to pilocarpine proved to be similar and a mathematical formula has been constructed to represent them. When testosterone propionate was administered in increasing quantities for periods of weeks at each level, the volume of the prostate increased in a series of flattened curves. This volume, under the conditions mentioned, was found to stand in a simple arithmetic relationship to the amount of testosterone propionate administered. Moderate quantities of testosterone propionate masked the effects of small amounts of stilbestrol on the prostate. The reverse was also true and the critical amounts of these compounds were defined. The amounts of stilbestrol were determined which lowered the quantity of prostatic secretion resulting from the simultaneous administration of moderate amounts of testosterone propionate in castrate dogs, the result being a level and flat secretory curve which was maintained for many weeks. We designate this effect the plateau phenomenon. When this amount of estrogen was continued, and the dosage of testosterone propionate greatly augmented, the prostatic secretion did not increase in volume. Very slight increases above the critical amount of stilbestrol, however, caused the secretory curve to fall to new and still lower levels though the secretion was never completely suppressed. The acid phosphatase content of the prostatic secretion in the regions of secretory plateaus was similar to that of castrate dogs injected with androgen alone. The plateau phenomenon is due to simultaneous physiologic action of androgenic and estrogenic compounds on the prostatic cells. The depression of prostatic secretion resulting in the plateau phenomenon is due to both functional and structural changes in the prostatic epithelium. They are best explained on the assumption that differences in steroid threshold exist in groups of cells within the prostate, those of the anterior rim of the gland being least susceptible to estrogenic activity.

Androgens↗