Effect of progestins, androgens, estrogens and antiestrogens on 3H-thymidine uptake by human endometrial and endosalpinx cells in vitro

The present study describes the effects of 11 steroid hormones and 3 non-steroidal antiestrogens on the 3H-thymidine uptake by human endometrial and endosalpinx cells in long-term cultures. The compounds were added in various concentrations ranging from 10(-9) to 10(-4) M. Progesterone and 19-nortestosterone caused a dose-dependent reduction of the 3H-thymidine incorporation resulting in a 94-98% inhibition at a concentration of 10(-4) M, gestonoroncaproate and d,1-norgestrel were less effective causing a 49% and 40% decrease. Antiproliferative effects were also noted after the addition of androgens (testosterone, 5 alpha-dihydrotestosterone, 5 beta-dihydrotestosterone and danazol). The inhibitory effect of testosterone was equivalent to progesterone at concentrations of 10(-4) M. The addition of estrogens (estrone, estradiol-17 beta and estriol) and antiestrogens (tamoxifen, N-desmethyl- and 4-OH-tamoxifen) produced a dual response in monolayer cultures as low concentrations (10(-9)-10(-6) M) were associated with a slightly increased 3H-thymidine incorporation while pharmacological concentrations (10(-5)-10(-4) M) were followed by a significant decrease. Cells originating from the endosalpinx did not respond to either estradiol-17 beta or progesterone. These results suggest that in contrast to endometrium, the proliferation of endosalpinx cells is independent of sex steroids.     

Prüfung praktisch-chirurgischer Lehre auf Distanz – Erfahrungen mit einem Hybrid-OSCE in der Chirurgie

Die Chirurgie - Die COVID-19-Pandemie hat die medizinische Lehre weltweit verändert. Digitale Lehrformate und Prüfungen konnten für kognitive Lernziele häufig gut eingesetzt...     

Grenzüberschreitung in der reproduktiven Medizin

Pregnancy risks after ovum donation (OD) to patients with ovarian failure or idiopathic low ovarian response are still under debate. As OD is prohibited in Germany by the embryo protection act couples wanting children contact in vitro fertilization (IVF) centres abroad sometimes without adequate information. The fear of stigmatization and uncertainties about the legal situation may lead patients to conceal the treatment abroad from their local physician. There is increasing evidence that OD is associated with pregnancy-induced hypertension. We here report on a 41-year-old patient who was admitted to this hospital in 2011 in the 24 0/7 week of gestation with manifest preeclampsia. As the patients condition worsened pregnancy was terminated in the 28^th week of gestation. The historical, ethical and legal aspects as well as the risks of preeclampsia after OD are discussed. Gynecologists should be aware of the risk of preeclampsia after OD and pregnancies have to be carefully observed.     

The cardiac troponin C mutation Leu29Gln found in a patient with hypertrophic cardiomyopathy does not alter contractile parameters in skinned murine myocardium

The present study investigates the effects of the first mutation of troponin C (hcTnC^L29Q) found in a patient with hypertrophic cardiomyopathy (HCM) on force–pCa relations and the interplay with phosphorylation of sarcomeric PKA substrates. In triton-skinned murine cardiac fibers, the endogenous mcTnC was extracted and the fibers were subsequently reconstituted with recombinant wild-type and mutant hcTnC. Force–pCa relations of preparations containing hcTnC^L29Q or hcTnC^WT were similar. Incubation of fibers reconstituted with the recombinant proteins with phosphatase to dephosphorylate sarcomeric PKA substrates induced an increase in Ca²⁺ sensitivity, slightly more pronounced (0.04 pCa units) in hcTnC^L29Q-containing fibers. Incubation of the dephosphorylated fibers with PKA induced significant rightward shifts of force–pCa relations of similar magnitude with both, hcTnC^L29Q and hcTnC^WT. No significant effects of hcTnC^L29Q on the velocity of unloaded shortening were observed. In conclusion, no major differences in contractile parameters of preparations containing hcTnC^L29Q compared to hcTnC^WT were observed. Therefore, it appears unlikely that hcTnC^L29Q induces the development of HCM by affecting the regulation of Ca²⁺-activated force and interference with PKA-mediated modulation of the Ca²⁺ sensitivity of contraction.     

Das ovarielle Überstimulationssyndrom

The ovarian hyperstimulation syndrome (OHSS) renders a severe iatrogenic condition, which occurs in 0.3–5.0 % of stimulated cycles. The risk for OHSS can be reduced by carefully scrutinizing stimulated cycles. However, it cannot be completely avoided. It is negligent not to monitor cycles stimulated with gonadotropins or clomiphene citrate. Dosages of gonadotropins or clomiphene citrate should be as low as possible. The assumption is wrong that acceptable pregnancy rates can only be achieved with attendant OHSS. In any case, the physical health of the patients is of paramount importance.     

RU 486 (mifepristone): induction of dose dependent elevations of estradiol receptor in endometrium from ovariectomized monkeys

This study was designed to investigate the effect of the anti-progestin RU 486 on estradiol receptor concentrations in the endometrium of monkeys given physiologic estrogen replacement therapy. Estradiol-17 beta (E2) silastic implants were inserted infrascapularly into 12 long-term ovariectomized cynomolgus monkeys (Macaca fascicularis) resulting in an average peripheral serum level of approximately 100 pg/ml estradiol. On day 6 of E2 treatment four treatment groups were initiated: Group I--estradiol implants only; Group II--estradiol implants plus 11 mumol progesterone/kg bodyweight in sesame oil via im injections on days 6,7,8; Group III--estradiol implants plus 2.2 mumol RU 486/kg in sesame oil via im injections on day 6,7,8; Group IV--estradiol implants plus 11 mumol RU 486/kg via im injections on day 6,7,8. On treatment day 9 endometrial biopsies were removed by hysterotomies. Cytosolic and nuclear estradiol receptor contents of tissues were estimated by charcoal method. In Group I, the tissue contained 376 +/- 123 pmol bound H-E2/g protein; the nuclear portion was about 16%. In Group II, the tissue contained 216 +/- 64 pmol bound 3H-E2/g protein; the nuclear portion was only 8%. In Group III, tissue contained 654 +/- 47 pmol bound H-E2/g protein; the nuclear portion was about 22%. In Group IV, the tissue contained 1198 +/- 172 pmol bound 3H-E2/g protein; the nuclear portion was about 17%. Scatchard plot analysis indicated a Kd app of 1.04 x 10(-9) M. This study demonstrates that after physiologic E2 replacement therapy estradiol receptor concentrations rise dramatically following anti-progestin treatment; this effect was dose dependent.     

Physiologie des ovariellen Zyklus

The menstrual cycle is mainly regulated by local and paracrine mechanisms. In particular the pituitary ovarian axis and the secretion of gonadotrophins depends on ovarian factors. The main role of gonadotrophins on anormal, cyclic function is a permissive one.