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PubMed1979

Oral contraceptives.

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Contraceptives, Oral↗
PubMed1988

[Growth inhibition by progestins in human endometrial cancer cells with progesterone receptors].

The presence of estrogen-independent progesterone receptors (PR) was demonstrated in a subline of a human endometrial cancer cell line, Ishikawa cells. Scatchard plot analysis of cytoplasmic binding data in a subline (IK-90) revealed a high affinity binding site for promegestone (Kd, 1.0 nM) with maximum binding sites of 158 fmol/mg protein. Competition experiments showed a binding specificity similar to that of typical PR. By low-salt sucrose gradient centrifugation, radioactive 8S and 4S peaks were found. The addition of 1 microM progesterone in culture medium resulted in a rapid nuclear translocation of cytoplasmic PR. Accumulation of glycogen in cytoplasm of the cells in response to 0.1 microM promegestone was observed by periodic acid-Schiff staining. Addition of various concentrations (1 nM-1 microM) of promegestone reduced the cell growth in a dose-dependent manner. The growth inhibition by promegestone was totally prevented by the concomitant addition of equimolar RU 486, a progestin antagonist. The other steroids including tamoxifen, cortisol, and testosterone had no significant effects on the growth of the cells. The growth-inhibitory effect of progestin on cultured cancer cells from human endometrial adenocarcinomas obtained by hysterectomy was also investigated. Addition of medroxyprogesterone acetate (1 nM-1 microM) caused a marked decrease in [3H]thymidine incorporation in cultured cancer cells from tumors with PR. From the viewpoint obtained in the present studies using both IK-90 cells and endometrial cancer cells in primary culture, it can be concluded that progestins produce regression of endometrial cancer directly via the PR system.

Cell Division↗
PubMed1982

Relationship between structure and mode of action of 16 alpha, 17 alpha-cycloalkanoprogesterones (pregna-D'-pentaranes).

A new class of modified progesterones with an additional 16 alpha, 17 alpha-carbocycle (pregna-D'-pentaranes) is obtained. These compounds were found to exhibit a high progestational activity in the Clauberg-McPhail assay and to be active as well in the pregnancy maintenance test in ovariectomized rabbits. Some of the pentaranes displayed a remarkable contraceptive effect in combination with mestranol. X-Ray data were employed for the description of molecular conformations of D'-pentaranes. On this base, their biological responses are considered to be connected with the conformational changes of D and D' rings as well as 17 beta-acetyl side chain. Accordingly, the contraceptive effect of D'3-6-pentaranes is correlated with the value of C(15)-C(16)-C(17)-C(20) torsion angle of the corresponding molecules. The relative binding affinities of some D'6-pentaranes to the progestin receptor were determined and compared with their in vivo biological responses.

Animals↗
PubMed1978

Reduction in incidence of rheumatoid arthritis associated with oral contraceptives. Royal College of General Practitioners' Oral Contraception Study.

Analyses of the frequency of reporting of rheumatoid arthritis have been undertaken as part of the continuing major prospective survey of oral contraceptives. The rate of reporting in oral-contraceptive users (takers) is half of the rate in non-users (controls). The rates for ex-takers and controls are not materially different. The expected rise in the rate of reporting in women over 35 is apparent in controls but suppressed in takers. In the absence of any accountable bias, it is concluded that oral contraceptives protect against the development of rheumatoid arthritis. Although the effect is small, the observation may be valuable in understanding the aetiology of the disease and the mechanism of action of oral contraceptives.

Adult↗
PubMed1994

[Metabolism and pharmacokinetics of synthetic estrogens and progestogens].

Synthetic steroids, having delta 4-3-ketone structure, are commonly metabolised to the corresponding tetrahydro-metabolites. The reduction of the 20-ketone group is also essential for pregnan series progestogens. When these metabolic pathways are obstructed in some way, steroids are hydroxylated at proper positions. Hydroxylation of a steroid is primarily directed to form the inactive form, namely, conjugated steroid. However, in some cases, it induces activation or activity change to the original compound. Activation of lynestrenol, as a progestogen and the conversion of norethindrone to ethynylestradiol, are examples. Metabolism of some new steroids and factors affecting the effect of oral contraceptive pills are discussed.

Estradiol Congeners↗
PubMed1977

[Thrombosis of the intracranial venous sinuses after ingestion of estroprogestative agents. 4 cases].

The authors report 4 cases of thrombosis of the superior longitudinal sinus (SLS) in women taking oestroprogestational agents. This complication is very rare, only 25 cases existing in the literature. The clinical picture consists of premonitory headaches associated with neurological signs suggesting lesions affecting both hemispheres in alternation. In the absence of treatment, sudden deterioration on about the tenth day is to be feared. This picture is similar to that of puerperal thrombosis of the SLS. The diagnosis should be confirmed by carotid arteriography, which demonstrates the presence of collateral varices and the thrombosed sinus giving a "negative" image on the AP view. Cerebral scintigraphy shows one or more areas of uptake in the form of adjacent rounded shapes, corresponding to cerebral infarctions of venous origin. As far as the responsibility of oestro-progenstational agents is concerned, the role is suggested by the analogy with puerperal thromboses and also by the absence of cases in men (with the exception of head injury, infections of the face and haematological malignancies). The prognosis is grave (19 deaths out of 29 cases), but surviving patients are completely cured. This prognosis would seem to be essentially dependent upon the possibilities of venous callateral circulation, which are variable in each individual patient. Anticoagulants and thrombolytic risk, in effective doses, to transform the venous thrombosis into a cerebral haemorrhage. Treatment consists rather of methods to reduce cerebral volume, aimed at maximal use of collateral varices and assisting the patient to overcome to acute phase of the first 2 weeks. Headache would seem to be the principal presenting symptom. In our opinion, no biological test gives a reliable indication as to those women most at risk and contraindictions are in fact of a clinical character.

Adult↗
PubMed1984

Progestin-specific markers in human cell lines: biological and pharmacological applications.

We review the progestin-specific responses (induced proteins, increased enzymatic activity) described in uterus, mammary tumours and human breast cancer cell lines established from pleural effusions. Recent data from our laboratory using the T47D breast cancer cell line are then given. They include: (a) a general methodology for evaluating the specific effects of steroids on the production of [35S]methionine-labelled proteins released into the culture medium; (b) results concerning the specificity of regulation by the progestins of a 48 000 dalton protein secreted by T47D cells; (c) the evidence for androgen-specific proteins in the same cells; (d) A discussion of the criteria required to define the receptor responsible for a particular effect of steroids. Lastly, we consider the general interest of progestin-regulated proteins in cell culture for pharmacology and biology.

Breast Neoplasms↗