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Biomedical subjects

F Kuttenn

Publications and source records attributed to F Kuttenn.

At least 127 records · Page 7Linked to original sources

Effects of percutaneous estradiol and conjugated estrogens on the level of plasma proteins and triglycerides in postmenopausal women.

Percutaneous administration of estradiol (E2) is a new substitutive treatment for postmenopausal women. In order to compare hepatic action of percutaneous E2 with that of conjugated estrogens, 18 postmenopausal women were allocated at random to receive one of these two types of natural estrogens for 21 days. Eight patients (group I) received conjugated estrogens orally, 1.25 mg daily. Ten patients (group II) were told to apply percutaneous E2 ointment, 5 gm (i.e., 3 mg of E2), each evening on the abdominal skin. E2, estrone (E1), follicle-stimulating hormone (FSH), and luteinizing hormone (LH), and several markers of estrogen action were evaluated before and after treatment. Both types of treatment were biologically effective, as indicated by the decrease in plasma gonadotropins and the increase in estrogen levels. However, conjugated estrogens produced a greater increase in E1 than in E2; hence, the E2/E1 ratio was 0.57 in group I, whereas it was approximately 1 in group II. Plasma renin substrate increased significantly (by 180%) in group I but not in group II. In the same way, conjugated estrogens produced a modest (12%) but significant decrease in antithrombin III, whereas there was no variation with percutaneous E2. Sex steroid-binding protein was the most sensitive parameter for the hepatic action of estrogen, and increased by 18.66% with percutaneous E2 and by 150% with conjugated estrogens. Plasma triglycerides tended to increase in group I and to decrease in group II, but not significantly. Therefore, percutaneous administration of of E2, in contrast to conjugated estrogens, can produce plasma levels of estrogens closer to those observed in the follicular phase and less alterations in protein synthesis. This lesser toxicity may be explained partially by the route of administration, since with percutaneous administration of E2, the steroid bypasses the liver.

Administration, Oral↗

Lupus nephropathy and pregnancy. Report of 104 cases in 36 patients.

The reciprocal influence of lupus nephropathy on the outcome of pregnancy and of pregnancy on the course of renal involvement was studied retrospectively in a series of 106 pregnancies observed during the past two decades in 36 patients with lupus nephropathy. The overall incidence of live births, corrected for induced abortions, was 54 (84%) in 64 pregnancies that began before clinical onset of systemic lupus erythematosus (SLE), 20 (87%) in 23 pregnancies that began after onset of SLE, and only four (57%) in seven cases where SLE was first manifested during or after gestation. Relapse or exacerbation of disease activity occurred in 12 (46%) of 26 pregnancies antedated by clinical onset of SLE, more frequently during gestation than post partum, with two cases (8%) of irreversible deterioration of renal function; clinical exacerbation of lupus disease was observed in 11 (66%) of 15 cases where SLE was clinically active at the time of conception, and in only one (9%) of 11 cases where SLE nephritis was in stable clinical remission for at least five months before conception. The data indicate that successful outcome of pregnancy may be expected even in the more severe forms of lupus nephritis if gestation begins after a sustained, complete clinical remission.

Abortion, Spontaneous↗

Influence of oral contraceptive therapy on the activity of systemic lupus erythematosus.

Since harmful effects of estrogens in murine lupus are well established, we studied the influence of oral contraceptive therapy on systemic lupus erythematosus activity in 26 female patients with lupus nephropathy. Combined preparations containing either 50 micrograms (14 patients) or 30 micrograms (7 patients) of ethinyl-estradiol were used in 21 courses in 20 patients. Initial manifestations or exacerbations of systemic lupus activity appeared within 3 months of beginning hormonal therapy in 9 patients, an overall incidence of lupus flare-up of 43%; there was major renal involvement in 4 patients. Conversely, evidence of lupus exacerbation did not develop in any of 11 patients who received pure progestogen oral contraceptive therapy with either continuous low-dose norsteroids (6 patients) or discontinuous progestogens at normal dosage (5 patients). These patients were followed for 5--30 months. Our data indicated that oral contraceptive therapy that used estrogens, even at low doses, often induced exacerbation of systemic lupus erythematosus activity. Pure progestogens, which were effective and devoid of such unfavorable effects, may be preferred in these patients.

Adolescent↗

Estradiol 17 beta-hydroxysteroid dehydrogenase activity in human breast fibroadenomas.

In the human endometrium, the presence of the progesterone-dependent enzyme 17 beta-hydroxysteroid dehydrogenase (E2DH) permits the conversion of an active estrogen, estradiol, into a less active one, estrone. This E2DH activity contributes to the antiestrogenic properties of progesterone. In the present study, E2DH activity was assayed in 54 surgically removed fibroadenomas. This benign breast disease was chosen since it offers rather homogeneous epithelial concentrations and still remains close to normal breast tissue from a pathological and hormonal point of view. E2DH activity was highest in fibroadenomas with high epithelial cell density. In addition, in these high epithelial cell density fibroadenomas (n = 18), E2DH activity increased markedly throughout the luteal phase of the menstrual cycle. Thus, it was 3- to 4-fold higher in fibroadenomas removed at the end of the luteal phase (1520 +/- 166 fmol/mg protein.h) than in those obtained during the follicular phase (375 +/- 95 fmol/mg protein.h). In addition, a striking increase in E2DH activity was observed in fibroadenomas from 5 patients treated with oral progestins (4080 +/- 650 fmol/mg protein.h) and 3 patients receiving progesterone topically applied upon the breast (3830 +/- 475 fmol/mg protein.h). E2DH activity, therefore, appears to be an important mechanism involved in the control by progesterone of estradiol action in breast tissue, as it is in the endometrium. It is also a good index of cellular differentiation and progesterone action at the molecular level. It is hypothesized that E2DH activity might be a specific marker of progesterone receptor itself and could be proposed in the evaluation of the hormone dependence of human breast tissue.

17-Hydroxysteroid Dehydrogenases↗

Androgen receptor in human skin cytosol.

Human skin, an accessible tissue, is an androgen target organ. We have measured the androgen-binding capacity of human skin cytosol using either 5 alpha[3H]dihydrotestosterone ([3H]DHT) or [3H]methyltrienolone ([3H]R-1881) as ligand. Samples were incubated for 20 h at 0 C, and dextran-coated charcoal was used to separate bound from free steroids. The androgen receptor has a high affinity for both ligands (0.23 +/- 0.04 nM for [3H]DHT; 0.32 +/- 0.16 nM for [3H]R-1881). Testosterone, cyproterone acetate, and, to a lesser extent, estradiol also bind this protein. Progesterone displaces R-1881 from its binding sites, whereas its 5 alpha-reduced metabolite somewhat inhibits DHT binding. The highest binding capacity is measured in cytosol of skin from external genitalia (129.14 +/- 58.0 fmol/g skin; n = 34); it is lower in pubic skin (21.8 +/- 13 fmol/g skin; n = 6). There is no variation as a function of age or sex in genital skin; the higher concentrations observed in the cytosol of pubic skin of women compared to that of men are probably related to lower levels of endogenous steroids. Whereas most patients with the complete form of the testicular feminization syndrome do not have detectable concentrations of androgen receptor, one patient with apparent complete clinical androgen insensitivity had a normal androgen-binding capacity. The parity of values in genital skin from men and women, the absence of variation with age, and the presence of a cytosolic androgen receptor in some androgen-insensitive patients suggest that the androgen receptor in human skin cytosol is not regulated by androgens.

Adolescent↗

Estradiol and progesterone receptors in human breast fibroadenomas.

Estradiol and progesterone receptors (ER and PR) were studied in 46 breast fibroadenomas obtained at different periods of the menstrual cycle (n = 38) or from patients under combined estrogen-progestagen contraceptive (n = 4) or substitutive progestagen treatment for progesterone insufficiency (n = 4). Cytosolic and nuclear ER (ERc and ERn) increased throughout the follicular phase and were at their maximal level in the preovulatory phase. They decreased during the luteal phase. PR levels were high in the follicular phase, especially in the cytosol (PRc). PRc then decreased while nuclear progesterone receptor (PRn) increased at the beginning of the luteal phase. Thereafter, PRc and PRn decreased and remained low during the luteal phase. PRc and PRn levels in fibroadenomas from patients under estrogen-progestagen therapy were similar to those found during the luteal phase of untreated patients. In patients receiving a substitutive progestagen treatment to correct progesterone insufficiency, PRn was markedly higher than PRc. The existence of ER and PR in breast fibroadenomas and the variations in their levels during the menstrual cycle or under hormonal treatment provide valuable information on the hormone dependency of breast fibroadenoma.

Adenofibroma↗

Hirsutism.

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17-Ketosteroids↗

Testosterone 5 alpha-reductase activity of skin fibroblasts. Increase with serial subcultures.

Cultures of skin fibroblasts from different anatomical sites have been established and testosterone 5 alpha-reductase assayed after the 2nd, 6th and 12th subcultures. After the 2nd passage, 5 alpha-reduction of testosterone to both dihydrotestosterone and androstanediols correlated well with that measured in direct assays performed in total skin homogenates; this is an additional evidence that different types of skin have specific levels of testosterone 5 alpha-reductase activity. However, there was a marked increase in 5 alpha-reductase activity with successive subcultures (X4--5 between 2nd and 12th subcultures) in all the cell strains studied. This finding could explain why data concerning 5 alpha-reductase in cultured skin fibroblasts are often conflicting with those in skin homogenates. It emphasizes the necessity of performing enzyme assays after the same number of passages to allow comparison from strain to strain. Different hypotheses are discussed in order to explain such variations of 5 alpha-reductase in cultured human skin fibroblasts.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗