Effect of mifepristone and levonorgestrel on expression of steroid receptors in the human Fallopian tube

Abstract

It is likely that mifepristone or levonorgestrel in the future will find extended use for contraceptive purposes. It is therefore essential to characterize the modes of action of these compounds. To assess the effect on the human Fallopian tube, 24 women with regular menstrual cycles and proven fertility, admitted to the hospital for voluntary sterilization by laparoscopic technique, were randomly allocated to a control or one of two treatment groups. Treatments were given with either a single dose of 200 mg mifepristone or 0.75 mg levonorgestrel in two doses 12 h apart, on day LH+2. Surgery was performed on day LH+4 to LH+6. Steroid receptor expression was analysed by immunohistochemistry, Western blot and RT-PCR. In the controls, there was a higher concentration of progesterone receptors in the stromal cells in the isthmic region than in those in the ampullar region. Treatment with mifepristone increased the progesterone receptor concentration in epithelial and stromal cells and increased the estrogen receptor concentration in epithelial cells. No effect on steroid receptor concentration was found following levonorgestrel. The contraceptive effect of post-ovulatory mifepristone has previously been considered to be dependent on an effect on the endometrium. However an effect on the Fallopian tube could contribute to alter the peri-implantation milieu influencing fertilization and embryo development.

Nuclear progesterone receptor A and B isoforms in mouse fallopian tube and uterus: implications for expression, regulation, and cellular function

“…To determine the response to gonadotropins and induction of ovulation (62), immature female mice (30 mice in one experiment) were given a single injection of 5 IU eCG or saline (hormone vehicle). eCG was administered intraperitoneally for 24 or 48 h. In addition, some of the animals (40 mice in one experiment) were injected intraperitoneally with 5 IU eCG followed 48 h later with a single injection of 5 IU hCG (ip) for the indicated time (6,12,24, and 48 h). The fallopian tubes and uteri were grossly dissected free of contaminating tissue (e.g., adipose tissue) after mice were killed by decapitation.…”

“…Relative to ovary and uterus, earlier studies have demonstrated that specific binding sites for P 4 can be observed using the ligand-binding characteristic assay in human and rodent fallopian tubes, (37,45,52,53,73). Later reports have demonstrated that PR mRNA and protein expression can be detected by RT-PCR (6,50,66), Western blot analysis (6,66), and immunohistochemical localization (1,6,18,19,50,66). Although PR proteins display cyclic changes in human fallopian tubes during the menstrual cycle (1,73), PR protein isoforms expressed in the fallopian tubes, their regulation, and their role in tubular function are much less well understood.…”

Efecto del levonorgestrel como anticonceptivo oral de emergencia en la ovulación, el endometrio y los espermatozoides

“…De estos 22 artículos, publicados entre 1995 y el 2010, diez estuvieron diseñados para medir el efecto sobre la ovulación (8)(9)(10)(11)(12)(13)(14)(15)(16)(17) , doce el efecto sobre el endometrio (9,12,13,(18)(19)(20)(21)(22)(23)(24)(25)(26) y tres el efecto sobre los espermatozoides (27)(28)(29) . De estos estudios, nueve correspondían a ensayos clínicos (8,9,14,15,18,19,23,24,27) , ocho a estudios cuasi-experimentales (10)(11)(12)(13)16,25,26,29) , tres a estudios observacionales (17,22,28) y dos a estudios in vitro (20,21) .…”

“…De estos estudios, nueve correspondían a ensayos clínicos (8,9,14,15,18,19,23,24,27) , ocho a estudios cuasi-experimentales (10)(11)(12)(13)16,25,26,29) , tres a estudios observacionales (17,22,28) y dos a estudios in vitro (20,21) . Tres estudios fueron hechos en animales (los tres correspondientes a diseños cuasiexperimentales (13,16,25) ) y el resto en humanos.…”

“…Los estudios realizados para evaluar si hay variación en los receptores endometriales posterior a la medicación con LNG no han demostrado diferencias con respecto a los grupos control (12,18,19,(21)(22)(23)(24) . Los principales receptores están relacionados con la progesterona.…”