RESUMO
Cortical cells of fetal rat adrenals in tissue culture were treated with 5-bromodeoxyuridine (BrdU) during their proliferative phase and during ACTH stimulation when nuclear DNA synthesis has almost ceased. Pretreatment with 0.5 mug/ml/day of BrdU inhibited the ACTH-induced differentiation of cortical cells as well as the secretion of corticosterone and 18-OH-deoxycorticosterone (18-OHDOC). When nuclear DNA synthesis was suppressed and mitochondrial DNA synthesis was stimulated by ACTH BrdU addition (30 mug/ml/day) permitted normal untrastructural differentiation of cortical cells, except that the development of mitochondrial inner membranes was inhibited. Simultaneously mitochondrial inner membranes was inhibited. Simultaneously mitochondrial 11beta- and 18-hydroxylations were strongly inhibited while cytoplasmic 21-hydroxylation was not affected.
Assuntos
Córtex Suprarrenal/ultraestrutura , Glândulas Suprarrenais/ultraestrutura , Hormônio Adrenocorticotrópico/farmacologia , Bromodesoxiuridina/farmacologia , Mitocôndrias/ultraestrutura , Córtex Suprarrenal/embriologia , Córtex Suprarrenal/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Corticosterona/metabolismo , DNA/biossíntese , Desoxicorticosterona/metabolismo , Morfogênese/efeitos dos fármacos , Progesterona/metabolismo , RatosRESUMO
The effects of corticosterone in concentrations found in adrenal venous plasma on ACTH-induced changes in cultured cortical cells derived from foetal rat adrenals were studied. Corticosterone at a concentration of 5-7 X 10(-5) mol/l completely inhibited mitochondrial differentiation to fasciculte-like morphology. The same cultures revealed significant inhibition of 11beta- and 18-hydroxylation compared with cultures treated with ACTH only. This was shown by the reduced formation of corticosterone and 18-OH-deoxycorticosterone (48%, P less than 0-001) and simultaneous enhancement of deoxycorticosterone formation (33%, P less than 0-05) from added [4-14C]progesterone. Similar inhibition was observed when dibutyryl cyclic AMP replaced ACTH as an inducer of differentiation. Lower concentrations of corticosterone (1-2 X 10(-5) and 2-4 X 10(-5) mol/l) inhibited ACTH-stimulated formation of corticosterone and 18-OH-deoxycorticosterone from endogenous precursors. The results demonstrate that corticosterone regulates the stage of differentiation in cultured adrenocortical cells. The possible role of corticosterone in the regulation of growth and steroidogenic capacity of the adrenal cortex is discussed.
Assuntos
18-Hidroxidesoxicorticosterona/biossíntese , Córtex Suprarrenal/embriologia , Glândulas Suprarrenais/embriologia , Hormônio Adrenocorticotrópico/antagonistas & inibidores , Diferenciação Celular/efeitos dos fármacos , Corticosterona/farmacologia , Desoxicorticosterona/análogos & derivados , Córtex Suprarrenal/efeitos dos fármacos , Córtex Suprarrenal/ultraestrutura , Animais , Bucladesina/antagonistas & inibidores , Células Cultivadas , Corticosterona/biossíntese , Desoxicorticosterona/biossíntese , Hidroxilação , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/ultraestrutura , Progesterona/metabolismo , RatosRESUMO
OBJECTIVES: The aim of this study was to compare a new estradiol-desogestrel (E2-DG) regimen with an E2-norethisterone acetate (NETA) combination (Trisekvens) regarding the treatment of menopausal complaints, bleeding pattern, histology of the endometrium and the occurrence of adverse experiences. METHODS: A total of 310 peri-/postmenopausal women with climacteric symptoms were randomly allocated to oral sequential treatment with either the E2-DG combination (1.5 mg E2 for 24 days with 0.15 mg DG for the last 12 days followed by 1 placebo tablet for 4 days) or with the E2-NETA combination (Trisekvens, 2 mg E2 for 22 days with 1 mg NETA for the last 10 days followed by 1 mg E2 for 6 days). Treatments were administered double-blind for 12 cycles of 28 days. RESULTS: One hundred and four women, 48 in the E2-DG group and 56 in the E2-NETA group, discontinued the study due to bleeding irregularities and various adverse effects. Both treatments reduced menopausal symptoms and complaints effectively and almost equally. The alleviation of perspirations and the improvement of general fitness were more apparent (P = 0.009) during cycle 1 with the E2-NETA treatment but were greater (P < 0.02) during the last 9/10-12 cycles of E2-DG treatment compared to E2-NETA. Regular withdrawal bleeding appeared in 93% and 90% of the women during treatment with E2-DG and E2-NETA, respectively. Intermenstrual bleeding occurred in 8% of women receiving E2-DG and in 13% of women treated with E2-NETA. The corresponding figures for intermenstrual bleeding-spotting were 21% and 22%. Secretory endometrium was detected in 65% and 54% of the samples taken at the end of treatment with E2-DG and E2-NETA, respectively. No hyperplasia or atypia was found. No serious adverse events related to treatment occurred. CONCLUSIONS: Both regimens alleviated effectively menopausal complaints and did not induce hyperplasia of endometrium. The minor differences recorded between the two regimens were probably due to the differences in their composition concerning the amount of estradiol and its distribution along the cycle, the amount and type of progestin and the length of estradiol/progestin combination phase.
Assuntos
Climatério/efeitos dos fármacos , Desogestrel/uso terapêutico , Estradiol/uso terapêutico , Terapia de Reposição de Estrogênios , Menopausa/efeitos dos fármacos , Noretindrona/análogos & derivados , Congêneres da Progesterona/uso terapêutico , Administração Oral , Desogestrel/administração & dosagem , Desogestrel/efeitos adversos , Método Duplo-Cego , Hiperplasia Endometrial/prevenção & controle , Endométrio/efeitos dos fármacos , Endométrio/patologia , Estradiol/administração & dosagem , Estradiol/efeitos adversos , Terapia de Reposição de Estrogênios/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Noretindrona/administração & dosagem , Noretindrona/efeitos adversos , Noretindrona/uso terapêutico , Acetato de Noretindrona , Cooperação do Paciente , Aptidão Física , Placebos , Pós-Menopausa/efeitos dos fármacos , Congêneres da Progesterona/administração & dosagem , Congêneres da Progesterona/efeitos adversos , Sudorese/efeitos dos fármacos , Hemorragia Uterina/prevenção & controleRESUMO
OBJECTIVES: The aim of this study was to compare a new sequential estradiol-desogestrel (E2-DSG) hormone replacement regimen (Liseta) with one of the standard treatments i.e. estradiol valerate-medroxyprogesterone acetate (E2V-MPA) combination (Klimalet) regarding the alleviation of climacteric symptoms, vaginal bleeding pattern and the occurrence of adverse experiences. METHODS: In a multicenter study performed in Denmark, a total of 376 perimenopausal women with climacteric symptoms were randomly allocated to oral sequential treatment with either E2-DSG (1.5 mg E2 for 24 days with 0.15 mg DSG for the last 12 days followed by a placebo tablet for 4 days) (n = 186) or with E2V-MPA (2 mg E2V for 21 days with 10 mg MPA for the last 10 days) (n = 190). Treatments were administered, using a double-blind, double-dummy technique for 6 cycles of 28 days. RESULTS: Three hundred and seventeen women, 158 in the E2-DSG and 159 in the E2V-MPA group, completed six treatment cycles. Both treatments reduced menopausal symptoms rapidly and to a similar extent. Hot flushes were present in 88% of the women in both groups. After six treatment cycles, hot flushes were no longer present in 71 and 62% of the women in the E2-DSG and E2V-MPA group, respectively. Perspiration decreased from 80 to 65% in the E2-DSG group and from 82 to 63% in the E2V-MPA group. Mood disturbances were present in 82% of the women in the E2-DSG at baseline, and in 52% after six cycles. In the E2V-MPA group the corresponding figures were 68 and 42%, respectively. The bleeding pattern was comparable in both treatment groups. Regular withdrawal (expected) bleeding appeared in 90-92% and in 85-90% of the women in cycles 1-5 with E2-DSG and E2V-MPA, respectively. Irregular bleeding (including spotting) occurred in 15.2% of the women receiving E2-DSG and in 20.1% of the women treated with E2V-MPA in cycle 6. In both treatment groups there was a tendency of a slight decrease in blood pressure. Adverse events were in less than 10% in each group the reason to discontinue treatment. CONCLUSIONS: Both treatments effectively alleviated menopausal complaints and presented good cycle control. Bleeding pattern and mood disturbances appeared to be more favorable influenced by E2-DSG.
Assuntos
Climatério/efeitos dos fármacos , Desogestrel/uso terapêutico , Estradiol/análogos & derivados , Estradiol/uso terapêutico , Estrogênios Conjugados (USP)/uso terapêutico , Terapia de Reposição Hormonal/métodos , Acetato de Medroxiprogesterona/uso terapêutico , Congêneres da Progesterona/uso terapêutico , Administração Oral , Pressão Sanguínea/efeitos dos fármacos , Desogestrel/administração & dosagem , Desogestrel/efeitos adversos , Método Duplo-Cego , Estradiol/administração & dosagem , Estradiol/efeitos adversos , Estrogênios Conjugados (USP)/administração & dosagem , Estrogênios Conjugados (USP)/efeitos adversos , Feminino , Rubor/prevenção & controle , Terapia de Reposição Hormonal/efeitos adversos , Humanos , Acetato de Medroxiprogesterona/administração & dosagem , Acetato de Medroxiprogesterona/efeitos adversos , Menopausa/efeitos dos fármacos , Pessoa de Meia-Idade , Transtornos do Humor/prevenção & controle , Placebos , Congêneres da Progesterona/administração & dosagem , Congêneres da Progesterona/efeitos adversos , Sudorese/efeitos dos fármacos , Hemorragia Uterina/induzido quimicamenteRESUMO
Desogestrel is a strong progestogen with low androgenicity which has so far been used only in oral contraceptives. We studied the feasibility of administering desogestrel in combination with oestradiol as hormone replacement therapy (HRT). Thirty women received a sequential combination containing 1.5 mg micronised oestradiol (24 days) and 0.15 mg desogestrel (last 12 days of cycle) for 6 months. At that stage 6 of the women dropped out; the remaining 24 were studied for a total of 12 months. The treatment alleviated vasomotor symptoms effectively in all the women and induced regular withdrawal bleeding in 86% of them. Secretory changes were observed in the endometria of 16 of the 20 women with adequate endometrial samples assessed after 12 months of treatment. No signs of hyperplasia or atypia were found. Six months of treatment resulted in a decrease in the mean serum follicle-stimulating-hormone concentration from 66.2 (+/- 4.3, S.E.M.) to 23.3 (+/- 3.1) IU/l and a rise in the oestradiol and sex-hormone-binding globulin concentrations from 87.9 (+/- 13.7) to 233.1 (+/- 20.4) pmol/l and from 52.1 (+/- 4.6) to 70.2 (+/- 5.6) nmol/l, respectively. Testosterone levels decreased. There were significant reductions in serum total and low density lipoprotein (LDL) cholesterol and triglycerides. After 12 months of treatment high-density lipoprotein (HDL) cholesterol values did not differ significantly from the pretreatment levels. The HDL/LDL and HDL/total cholesterol ratios increased. The treatment reduced bone turnover as indicated by decreases in bone alkaline phosphatase and osteocalcin serum levels and by lowered urinary calcium/creatinine and hydroxyproline/creatinine ratios. An increase of about 2% in forearm bone mineral density was also observed. This new oestradiol-desogestrel preparation therefore appears to be a promising alternative form of HRT. It alleviates climacteric symptoms effectively, exhibits favourable effects on serum lipids and lipoproteins and prevents bone loss.
Assuntos
Desogestrel/farmacologia , Terapia de Reposição de Estrogênios , Densidade Óssea/efeitos dos fármacos , Climatério/efeitos dos fármacos , Desogestrel/efeitos adversos , Endométrio/citologia , Endométrio/efeitos dos fármacos , Feminino , Hormônios/sangue , Humanos , Lipídeos/sangue , Pessoa de Meia-IdadeAssuntos
Corpo Lúteo/metabolismo , Congêneres da Progesterona/farmacologia , Progesterona/biossíntese , Alilestrenol/farmacologia , Didrogesterona/farmacologia , Estrenos/farmacologia , Feminino , Humanos , Técnicas In Vitro , Linestrenol/farmacologia , Medroxiprogesterona/farmacologia , Megestrol/farmacologia , Noretindrona/farmacologia , Noretinodrel/farmacologia , Norgestrel/farmacologia , Gravidez , Primeiro Trimestre da GravidezRESUMO
Testicular steroid metabolism of winter and spring frogs, Rana temporaria, were studied by in vitro incubation with radioactively labelled dehydroepiandrosterone and androst-4-ene-3,17-dione. Marked seasonal differences were observed which are in line with the findings of others.
Assuntos
Androgênios/metabolismo , Androstenodiona/metabolismo , Desidroepiandrosterona/metabolismo , Estações do Ano , Testículo/metabolismo , Animais , Anuros , Masculino , NAD/farmacologia , Rana temporaria , Testosterona/metabolismoRESUMO
Villous tissue from 26 placentae of 7-17 weeks was incubated with radioactive pregnenolone alone and with pregnenolone in the presence of progesterone and 9 synthetic gestagenic steroids and the progesterone formation was measured after 30 min. When progesterone was present in a concentration of 31 or 310 mumol/1 the conversion rate of labelled pregnenolone to progesterone was reduced to 88.6 and 82.2% of that of the respective control incubations. Dydrogesterone, allyloestrenol, lynoestrenol and norethynodrel under similar conditions did not inhibit the formation of progesterone. The inhibitory effects of megoestrol acetate, medroxyprogesterone acetate and norgestrel were close to that of progesterone. Norethisterone and methyloestrenolone were the most effective inhibitors of progesterone formation: when incubated in an equimolar concentration (35 mumol/1) with pregnenolone (50 microgram) the progesterone formation was reduced to 60.0-62.7% and 29.1-34.0% respectively of that of the respective control experiments.
Assuntos
Vilosidades Coriônicas/efeitos dos fármacos , Placenta/efeitos dos fármacos , Pregnenolona/metabolismo , Congêneres da Progesterona/farmacologia , Progesterona/biossíntese , Alilestrenol/farmacologia , Vilosidades Coriônicas/metabolismo , Didrogesterona/farmacologia , Estrenos/farmacologia , Feminino , Humanos , Técnicas In Vitro , Linestrenol/farmacologia , Medroxiprogesterona/farmacologia , Megestrol/farmacologia , Nandrolona/farmacologia , Noretindrona/farmacologia , Norgestrel/farmacologia , Gravidez , Primeiro Trimestre da GravidezRESUMO
To study the role of vasodilatory prostacyclin and vasoconstrictory thromboxane A2 in climacteric vascular instabilities, overnight urine samples were collected from sixteen women suffering from hot flushes and sweating before, during and after the six months' cyclic estradiol-desogestrel therapy as well as from ten non-climacteric control women. The urine was assayed for 6-keto-PGF1a and 2,3-dinor-6-keto-PGF1a (metabolites of prostacyclin) as well as for thromboxane B2 and 2,3-dinor-thromboxane B2 (metabolites of thromboxane A2) by means of HPLC and radioimmunoassay. No difference was seen in baseline prostaroid output between the climacteric and non-climacteric study groups. Furthermore, no relation was observed between individual prostanoid excretion and severity of vasomotor symptoms before replacement therapy. The replacement therapy abolished or markedly alleviated hot flushes and sweating, but prostanoid output did not change. Our data imply that climacteric symptoms are not accompanied by changes in the production of prostacyclin and thromboxane A2.
Assuntos
Climatério/urina , Epoprostenol/metabolismo , Terapia de Reposição de Estrogênios , Tromboxano A2/metabolismo , Tromboxano B2/urina , 6-Cetoprostaglandina F1 alfa/análogos & derivados , 6-Cetoprostaglandina F1 alfa/urina , Adulto , Cromatografia Líquida de Alta Pressão , Estradiol/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Progestinas/uso terapêutico , Radioimunoensaio , Tromboxano A2/urina , Tromboxano B2/análogos & derivadosRESUMO
Mouse preimplantation embryos were incubated with radioactive pregnenolone, progesterone or dehydroepiandrosterone for various periods of time. These substrates were not converted to metabolites even after incubation of 120 h. We suggest that preimplantation mouse embryo does not possess enzyme activities for steroid metabolism.
Assuntos
Embrião de Mamíferos/metabolismo , Esteroides/metabolismo , Animais , Desidroepiandrosterona/metabolismo , Desenvolvimento Embrionário , Feminino , Técnicas In Vitro , Camundongos , Gravidez , Pregnenolona/metabolismo , Progesterona/metabolismoRESUMO
PIP: 39 women were randomly allocated to contraception with either a combined oral contraceptive (ethinyl estradiol 37.5 mcg + lynestrenol 0.75 mg=EE + LYN), a progestin-only preparation (lynestrenol 0.5 mg daily=LYN), or a copper containing IUD. Pretreatment and 1, 3, and 6 month treatment blood samples were obtained and assayed for serum cholesterol, triglycerides, and high density lipoprotein (HDL) cholesterol. In the subjects using EE+LYN, the HDL cholesterol/cholesterol ratio was significantly (P0.01) elevated after 6 months treatment. Also, triglycerides increased significantly (P0.01). In the LYN group, no significant alterations in the lipid parameters occurred. In the IUD group, cholesterol levels decreased significantly (P0.05) and a significant (P0.01) rise in HDL-cholesterol/cholesterol ratio was seen. Triglyceride levels did not change. The results obtained suggest that the low-dose EE+LYN and LYN OCs do not induce such changes in serum lipids that could be related to the risk of development of atherosclerosis. The decrease in cholesterol levels during IUD use remains to be confirmed by other further studies.^ieng
Assuntos
Anticoncepção , Anticoncepcionais Femininos , Anticoncepcionais Orais , Cobre , Doença , Compostos Inorgânicos , Dispositivos Intrauterinos , Lipídeos , Metabolismo , Metais , Congêneres da Progesterona , Biologia , Fenômenos Químicos , Química , Anticoncepcionais , Etinilestradiol , Serviços de Planejamento Familiar , Hormônios , Linestrenol , Fisiologia , Substâncias para o Controle da ReproduçãoRESUMO
12 women using a low-dose combination oral contraceptive (OC) and 17 wearing a copper IUD were studied. Serum ferritin concentrations were measured before and 1, 3, and 6 months after commencing contraception. Ferritin levels in the iron-deficient range (below 50 mcg/l) were present in 5 (42%) and in 8 (47%) subjects, respectively, prior to the start of OCs or IUD insertion. The OC use induced only a temporary decrease in serum ferritin levels at the start of treatment, whereas 12 of 17 (71%) IUD users had reached iron-deficient levels by the end of the follow-up period. Thus, the use of OCs had no adverse effect on iron balance, but the monitoring of iron status and the administration of iron-replacement therapy seem to be indicated in the majority of women fitted with an IUD.