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Biomedical subjects

F Kuttenn

Publications and source records attributed to F Kuttenn.

At least 73 records · Page 4Linked to original sources
PubMed1991

Selective venous catheterization in the evaluation of hyperandrogenism.

Retrograde bilateral ovarian-adrenal vein catheterization was carried out in 16 patients with plasma testosterone levels exceeding 1.4 ng/ml (4.85 nmol/l). While pelvic ultrasonography and computerized axial tomographic scan failed to locate the androgen-producing ovarian tumors, catheterization led to a diagnosis of occult ovarian tumor in 5 patients, based on the observation of an abnormally-high and unilateral ovarian-peripheral vein testosterone gradient, which was subsequently confirmed histopathologically. In one case, unilateral elevation of the adrenal-peripheral vein testosterone gradient was found, complementing the ultrasonographic finding of an adrenal mass and confirming the diagnosis of a virilizing adrenal tumor. In the other 10 patients, gradient analysis ruled out an androgen-producing tumor, leading to the identification of nontumoral hyperandrogeny, such as a severe form of the polycystic ovary syndrome in the 6 premenopausal patients and of ovarian stromal and hilus cell hyperplasia in the 4 menopausal patients. In conclusion, appropriate indication of selective catheterization may considerably reduce the need for exploratory surgery and may help in selecting the adequate surgical approach.

Adrenal Gland Neoplasms↗
PubMed1991

17 beta-estradiol dehydrogenase (E2DH) activity in T47D cells.

Activity of NAD-dependent 17 beta-hydroxysteroid dehydrogenase (E2DH), the enzyme which converts estradiol (E2) into its less active metabolite estrone (E1), has been previously characterized in normal human breast cells in culture and in benign and malignant breast tumors. E2DH activity is far greater in epithelial cells than in fibroblasts. Moreover, it is progesterone dependent in epithelial cells. It was therefore interesting to explore E2DH in the progesterone receptor (PR)-rich T47D cell line as a possible marker of hormone dependence in breast cancer cells. In T47D cells, transformation of [3H]E2 to E1 is limited. The metabolism seems to be preferentially oriented in the way E1----E2 in these cells. However, in the presence of the cofactor NAD the conversion of E2 into E1 increases. Moreover, treatment of T47D cells in culture by the progestin R5020 stimulates E2 to E1 conversion 2- to 3-fold. Stimulation of E2DH (E2----E1) activity reflects both the presence and the operability of PR. This observation underlines the possible interest of E2DH assay in parallel to estradiol receptor and PR to evaluate hormone-dependence of breast cancer.

Breast Neoplasms↗
PubMed1991

Estradiol and progesterone receptors in cultured normal human breast epithelial cells and fibroblasts: immunocytochemical studies.

The estradiol (E2) and progesterone (P) receptors (ER and PR) were studied in normal human breast epithelial (HBE) cells and fibroblasts cultured separately in our laboratory from surgical reductive mammoplasty samples. Immunocytochemical studies were performed on cytospun cells using the anti-ER antibody H222 Sp gamma and the anti-PR antibodies JZB39 and KD68. A specific immunostaining was observed for ER and PR in HBE cells. This immunostaining was nuclear, varying from cell to cell in positivity and intensity of staining. Moreover, ER and PR immunostaining was hormone-modulated: it increased in E2-treated cells and decreased after addition of the progestin R5020. In fibroblasts, a weak ER immunostaining and a stronger PR immunostaining could be observed; however it was not modified by either E2 or progestogen treatment. Thus, in normal breast epithelial cells, E2 stimulates both its own receptor and PR, whereas the progestin R5020 lowers ER and PR content. In contrast, ER and PR content in normal breast fibroblasts seem to be independent of E2 or P action.

Adolescent↗
PubMed1991

Distribution of deletions and seven point mutations on CYP21B genes in three clinical forms of steroid 21-hydroxylase deficiency.

To characterize mutations in the CYP21B gene that are responsible for congenital adrenal hyperplasia (CAH), DNA samples from 91 French patients have been studied by allelic-specific oligonucleotide hybridization and Southern blot analysis. Seven sites mostly found in the CYP21A pseudogene and deletions of the functional CYP21B gene have been screened. Gene conversions involving small DNA segments accounted for 57% of the tested mutations and probably cause 74% of the mutations responsible for the disease. Complete deletion of the CYP21B gene accounted for 18% of the CAH mutations in the whole sample and for 21% in the classical form of the disease. Three mutations were found associated with specific clinical forms of the disease: a G-C substitution in the seventh exon was associated with the late-onset form of the disease, and both an 8-bp depletion in the third exon and complete deletion of CYP21B were associated with the salt-wasting form.

Adrenal Hyperplasia, Congenital↗
PubMed1990

Cyproterone acetate versus hydrocortisone treatment in late-onset adrenal hyperplasia.

Thirty late-onset adrenal hyperplasia patients consulting for isolated hirsutism were randomly divided into two groups; group 1 (n = 16) was treated with hydrocortisone in order to suppress androgen adrenal secretion, and group 2 (n = 14) received cyproterone acetate (CPA) antiandrogen therapy to inhibit peripheral androgen activity. The clinical and hormonal effects of each type of treatment were evaluated. Before treatment, the clinical and hormonal profiles of the two patient groups did not differ significantly. Excellent clinical evolution in terms of the regression of hirsutism was observed in the CPA-treated patients (54% decrease in the clinical score in 1 yr), in contrast with the slight decrease in hirsutism (26%) after hydrocortisone treatment. In hydrocortisone-treated patients, plasma androgen decreased to normal levels: testosterone from 3.05 +/- 1.45 to 1.46 +/- 0.42 nmol/L and delta 4-androstenedione from 13.6 +/- 4.1 to 6.33 +/- 1.47 nmol/L. Conversely, in CPA-treated patients, only a slight decrease in testosterone from 2.98 +/- 1.98 to 2.29 +/- 0.64 nmol/L and in delta 4-androstenedione from 12.9 +/- 5.9 to 9.86 +/- 2.23 nmol/L was observed. This slight decrease in plasma androgens contrasts with the rapid clinical improvement after CPA. These results emphasize the importance of peripheral receptivity to androgens in the clinical expression of hyperandrogenism. Moreover, they indicate that peripheral antiandrogen therapy may be more appropriate in late-onset adrenal hyperplasia patients than conventional adrenal inhibition using cortisone therapy.

Adolescent↗
PubMed1990

[Hormonal contraception and lupus].

The choice of an optimal contraceptive method (OC) therapy is a significant problem in female SLE patients. In view of the influence of sex hormones on the evolution of SLE, oral contraceptive (OC) therapy has to be efficient, reversible and safe, without aggravating disease activity and causing metabolic and vascular side effects. Ethinyl estradiol-containing preparations, even at 30 micrograms/day, have been shown to trigger a crisis or unmask SLE, and they exert adverse metabolic and vascular effects. Therefore, combination estrogen-progestogen compounds must be avoided in women with SLE. Pure progestogen OC preparations do not stimulate SLE activity, but norsteroids have harmful metabolic effects and microprogestogens are not sufficiently reliable. In light of the decreased level of plasma androgens in female SLE patients, an attempt to modulate the hormonal milieu by lowering the estrogen to androgen ratio, while ensuring contraception was attempted using cyproterone acetate. This agent markedly lowered plasma estrogens and was effective and well tolerated, but its long-term effect on bone mineralization remains to be evaluated. Chlormadinone acetate, a 17-OH progesterone derivative, was proven effective and devoid of any metabolic or vascular side effects, and should be recommended as the safest routine OC therapy in women with SLE.

Chlormadinone Acetate↗
PubMed1989

[21-deoxycortisol. A new marker of virilizing adrenal hyperplasia caused by 21-hydroxylase deficiency].

21-deoxycortisol is a steroid produced mainly by the adrenal gland. Its normal plasma baseline concentrations (0.03 to 0.30 n/ml) and its concentrations after tetracosactide injection (0.15 to 0.76 ng/ml) do not significantly vary with age, sex and phases of the menstrual cycle. 21-deoxycortisol was assayed in plasma by a specific radioimmunological method and its values were compared with those of 17-OH progesterone in heterozygous subjects with the classical and non-classical forms of 21-hydroxylase deficiency, and in the amniotic fluid of foetuses with this deficiency. Baseline concentrations of 21-deoxycortisol in the classical forms of 21-hydroxylase deficiency (n = 12; 55.36 to 186.6 ng/ml) and post-tetracosactide concentrations in non-classical late onset forms (n = 31; 4.04 to 47 ng/ml) were much higher than in normal subjects, thus making this steroid as sensitive as, or even more sensitive than 17-OH progesterone in diagnosing 21-hydroxylase deficiency. Post-tetracosactide assays of 21-deoxycortisol in 84 heterozygous subjects with 21-hydroxylase deficiency (0.70 to 5.40 ng/ml) enabled these subjects to be detected with a more than 90 percent sensitivity, which cannot be obtained with 17-OH progesterone assays. 21-deoxycortisol concentrations in the amniotic fluid of foetuses with 21-hydroxylase deficiency (n = 11; 0.391 to 0.930 ng/ml) were constantly superior to those observed in normal foetuses (n = 38; 0.034 to 0.221 ng/ml), so that the deficiency can be diagnosed with the steroid as easily as with 17-OH progesterone.

17-Hydroxycorticosteroids↗
PubMed1989

Testosterone-estradiol binding globulin (TeBG) in hirsute patients treated with cyproterone acetate (CPA) and percutaneous estradiol.

Testosterone-estradiol binding globulin (TeBG) was studied in 50 hirsute women, before and after 6-month treatment with cyproterone acetate (CPA). 50 mg CPA was administered orally from the 5th to the 25th day of the menstrual cycle and combined with 3 mg 17 beta-estradiol (E2) administered percutaneously from days 16-25 of the cycle. TeBG was evaluated by a filter assay measuring [3H]-DHT binding capacity. Before treatment, the mean plasma TeBG level was 40 +/- 12 nM in hirsute patients, which is significantly lower than TeBG value in normal women (60 +/- 9 nM, n = 20, P less than 0.01) and intermediate between normal women and normal men (30 +/- 8 nM, n = 20). After a 6-month treatment, TeBG strikingly decreased to 22 +/- 8 nM, which is significantly lower than pretreatment values (P less than 0.01) and even less than TeBG level in normal men. Parallel TeBG assay by immunoelectrodiffusion in 8 of these hirsute patients provided similar results. With this treatment, plasma testosterone and delta 4-androstenedione, measured between the 20th and 25th days of the cycle, decreased from 68 +/- 21 to 25 +/- 8 ng/dl, and 210 +/- 95 to 98 +/- 31 ng/dl respectively. Plasma estradiol decreased from 150 +/- 62 pg/ml to 75 +/- 25 pg/ml. In contrast, urinary 3 alpha-androstanediol glucuronide remained high: 112 +/- 51 and 123 +/- 55 micrograms/24 h respectively before and with CPA treatment. Three mechanisms have been proposed to explain TeBG decrease under CPA + E2perc. treatment (1) relative competition of CPA with labelled DHT in the TeBG-binding capacity assay, (2) relative hypoestrogenism with this treatment, (3) a progestagen or even a partial agonistic androgen effect of CPA on TeBG synthesis in the liver. The third mechanism appears to be predominant. In any case. TeBG decrease combined with the partial enzymatic induction effect of CPA on the liver contributes to the increase in the metabolic clearance rate of T and the high urinary Adiol levels previously reported with CPA treatment.

Adolescent↗
PubMed1989

Androgen receptor in sexual differentiation.

Androgens play an essential role in sexual differentiation and their action is mediated by the androgen receptor (AR). The normal AR is a soluble protein, highly thermolabile, with a mol. wt of 90 kDa and a pI of 5.2 as determined by 2 dimensional (2D) gel electrophoresis. It is regulated by androgens in culture conditions but the physiological relevance of this regulation remains controversial. The presence of a functional AR is an absolute requirement for male sexual differentiation and its absence results in complete insensitivity. However, androgen insensitivity (complete or partial) can develop in the presence of a normal androgen binding capacity and there is no correlation between the clinical and the biochemical findings. A number of qualitative abnormalities have been described to explain the failure of androgen action in these cases: they all emphasize the extreme instability of the abnormal AR. It is difficult at the present time to determine whether these abnormalities result from structural mutations of the AR gene, transcriptional or post-transcriptional abnormalities. Further elucidation of these defects awaits for an antibody and/or a cDNA probe for the AR.

Animals↗
PubMed1989

Increased plasma 21-deoxycorticosterone (21-DB) levels in late-onset adrenal 21-hydroxylase deficiency suggest a mild defect of the mineralocorticoid pathway.

Plasma 21-deoxycorticosterone (21-DB) concentrations were measured before (basal) and 1 h after ACTH stimulation in a population of 34 normal subjects, 18 patients with the late-onset form of congenital adrenal hyperplasia (LO-CAH) due to 21-hydroxylase deficiency, and 19 LOCAH heterozygotes. For comparison, plasma 21-deoxycortisol (21-DOF) and 17-hydroxyprogesterone (17-OHP) were determined simultaneously in the same subjects. Plasma 21-DB concentrations as well as those of 21-DOF did not vary significantly as a function of age, sex, or phase of the menstrual cycle, in contrast to plasma 17-OHP. The mean plasma 21-DB concentrations in normal subjects (adult men, follicular and luteal phase women, and children) were 19.0 +/- 9.5 (+/- SD) pmol/L before and 73.2 +/- 31.0 after ACTH stimulation. In the LOCAH patient group, the mean post-ACTH plasma 21-DB concentration was 1736.0 +/- 1243.0 pmol/L, and all values were above the highest post-ACTH value (148.2 pmol/L) in the normal subjects. Similarly, in the LOCAH patients the post-ACTH plasma 21-DOF concentration was 33.7 +/- 20.3 nmol/L, and the post-ACTH plasma 17-OHP value was 134.0 +/- 70.6 nmol/L; all LOCAH patients had supranormal responses to ACTH. However, 38.9%, 11.2% and 16.7% of the basal plasma 21-DB, 21-DOF, and 17-OHP values in the LOCAH patients overlapped those in the normal subjects. There was a rather large overlap (63.2%) in post-ACTH plasma 21-DB levels between the LOCAH heterozygotes and the normal subjects; it was less than the overlap in plasma 17-OHP (74%) and more than the overlap in plasma 21-DOF values (5.2%) in these same 2 groups. There was moderate overlap (21%) in the post-ACTH plasma 21-DB levels between the LOCAH heterozygotes and LOCAH patients, but no overlap between these 2 groups for either 21-DOF or 17-OHP. The abnormally elevated post-ACTH plasma 21-DB levels found in all the LOCAH patients as well as in some LOCAH heterozygotes suggest the existence of minor 21-hydroxylase deficiency in the mineralocorticoid synthetic pathway in these patients in addition to the well known impairment in the glucocorticoid pathway demonstrated by the elevated post-ACTH 21-DOF and 17-OHP levels.

17-alpha-Hydroxyprogesterone↗
PubMed1989

[Antiestrogens and normal human breast cell proliferation].

Steroidal (progestins) and non steroidal antiestrogens (tamoxifen and derivatives) are strong antiproliferative molecules when added to normal human breast cells in culture. The antiproliferative action of tamoxifen and 4-hydroxytamoxifen isomers is comparable to that observed in cultured breast cell lines. The progestin promegestone (R 5020) is a strong antiproliferative agent in the presence as well as in the absence of estradiol. Identically, at higher concentration the antiprogestin RU 486 slows down cell proliferation probably due to its progesterone agonist activity. Both progestins and antiprogestins stimulate 17 beta-hydroxysteroid dehydrogenase activity, a marker of progesterone receptor but only in estradiol primed cells.

17-Hydroxysteroid Dehydrogenases↗
PubMed1988

Tamoxifen and hydroxytamoxifen isomers versus estradiol effects on normal human breast cells in culture.

Estradiol and triphenylethylene antiestrogen actions have been studied extensively in breast cancer cell lines. However, their effects are still poorly understood on normal human breast cells. We have developed a culture system of normal human breast epithelial (HBE) cells. It has been shown previously that cultured HBE cells were hormone dependent and well adapted for the study of hormone/antihormone actions. However, until now, no data were available on estradiol receptor (ER) in HBE cells. In this study, the presence of ER was demonstrated by (a) whole-cell biochemical assay on breast cells after enzymatic tissue dissociation and (b) an immunocytochemical method using an anti-ER monoclonal antibody both on enzymatically dissociated cells and on 8-day cultured cells. Immunostaining was nuclear and cell positivity was heterogeneous. However, the percentage of positive cells and staining intensity were far greater in the presence of estradiol in the culture, indicating estradiol stimulation of ER. Moreover, HBE cells were used to study the action on cell growth of estradiol versus trans-tamoxifen (TAM), trans-4-hydroxytamoxifen (trans-4OHTAM), and cis-4-hydroxytamoxifen (cis-4OHTAM) alone or added to estradiol. Cell growth was estimated daily by a histometric method and by DNA assay at the end of the 7-day study. When the medium was minimally supplemented with human serum (1%), estradiol stimulated cell growth in a dose-dependent manner at concentrations varying from 10(-9) to 10(-7) M. TAM and trans-4OHTAM clearly inhibited mammary cell division when estradiol was added to the medium and, to a lesser extent, in the absence of estradiol. This inhibitory effect was dose dependent. trans-4OHTAM was 100 times more active than trans-TAM. cis-4OHTAM also clearly inhibited breast cell division at 10(-7) and 10(-6) M concentrations but was 3-fold less efficient than trans-4OHTAM. In conclusion, (a) the presence and estradiol dependence of ER have been demonstrated in HBE cells, which constitute a fruitful model for the study of hormone/antihormone actions, and (b) in these normal cells, estradiol stimulates growth, whereas TAM and the 4OHTAM isomers are potent inhibitors of cell multiplication, as they are in breast cancer cell lines in culture.

Breast↗
PubMed1988

[Pregnancy: a way of recovering from prolactin-secreting adenoma? 18 cases].

Fifteen patients with prolactin-secreting pituitary adenoma completed a total of 18 pregnancies. Changes in blood prolactin levels and computerized tomographic images of the pituitary gland were studied. No increase in size of the adenoma was observed, and in 2 cases the tumour was found to be necrotic in the post-partum period. In all patients the prolactinaemia significantly decreased immediately after delivery. Thus, by inducing partial necrosis of the adenoma pregnancy may result in post-partum reduction of blood prolactin levels.

Adult↗
PubMed1988

Comparison of basal and adrenocorticotropin-stimulated plasma 21-deoxycortisol and 17-hydroxyprogesterone values as biological markers of late-onset adrenal hyperplasia.

Plasma 21-deoxycortisol (21-DOF) and 17-hydroxyprogesterone (17-OHP) concentrations were assayed before (basal) and 1 h after ACTH stimulation in 4 groups of normal subjects (35 follicular phase women, 22 luteal phase women, 33 adult men, and 15 prepubertal children) and in a group of 31 patients with the late-onset form of congenital adrenal hyperplasia (LOCAH) due to 21-hydroxylase deficiency as well as in 31 LOCAH) heterozygotes. The mean basal plasma 21-DOF concentrations in each of the 4 groups of normal subjects were between 8 ng/dL (0.23 nmol/L) and 11 ng/dL (0.31 nmol/L), and they increased significantly after ACTH stimulation to between 36 ng/dL (1.04 nmol/L) and 44 ng/dL (1.27 nmol/L). There were no differences in basal or ACTH-stimulated plasma 21-DOF levels in these 4 groups, whereas their basal and post-ACTH plasma 17-OHP levels did vary. Among the LOCAH patients, 83.8% had basal plasma 21-DOF levels and 61.2% had basal plasma 17-OHP levels higher than the highest basal 21-DOF [30 ng/dL (0.86 nmol/L)] and 17-OHP [450 ng/dL (13.61 nmol/L)] concentrations in the normal subjects, and all individual 21-DOF and 17-OHP levels after ACTH stimulation [greater than or equal to 404 ng/dL (11.67 nmol/L) and greater than or equal to 1040 ng/dL (31.47 nmol/L), respectively] were markedly higher than the highest 21-DOF [76 ng/dL (2.19 nmol/L)] and 17-OHP [580 ng/dL (17.55 nmol/L)] levels in the normal subjects. The mean post-ACTH/basal plasma level ratios among the LOCAH patients were 19.75 for 21-DOF and 8.03 for 17-OHP. In LOCAH heterozygotes, basal 21-DOF values were higher than normal in 48.3%, and post-ACTH values were higher than normal in 93.5% of the cases. In contrast, basal plasma 17-OHP levels were similar in LOCAH heterozygotes and normal subjects, and only 16.1% of the LOCAH heterozygotes had post-ACTH plasma 17-OHP levels higher than the highest normal value. If sex and phase of the menstrual cycle are taken into account, along with the incremental responses (post-ACTH minus baseline value) of plasma 21-DOF and 17-OHP, to compare LOCAH heterozygotes and normal subjects, the discriminating power for detection of heterozygocity was somewhat increased for 21-DOF (to 100%) and appreciably increased for 17-OHP (to 30%).(ABSTRACT TRUNCATED AT 400 WORDS)

17-Hydroxycorticosteroids↗
PubMed1987

[Indications and results of pituitary radiotherapy after microsurgery in acromegaly. 15 cases].

The present treatment of acromegaly consists of selective adenomectomy followed, when unsuccessful, by pituitary gland irradiation. Fifteen acromegalic patients were evaluated after adenomectomy, then radiotherapy. Growth hormone assays were performed after carbohydrate load and administration of thyroid stimulating hormone. Somatomedins were measured by radiocompetition using the vector protein. Cure was obtained with adenomectomy alone in 3 of the 15 patients (mean follow-up 39 months). The remaining 12 patients were all cured by subsequent irradiation at the cost of pituitary insufficiency in one-third of them. Post-surgical cure of acromegaly can only be asserted from range of strict criteria. The best indicators of persisting activity are high levels of growth hormone and/or somatomedins. A solitary somatotropic dysregulation does not necessarily herald a relapse.

Acromegaly↗