Growth inhibition of fibroblasts by progesterone and medroxyprogesterone in vitro.

This study was carried out to evaluate in vitro the beneficial effects observed in various aggressive fibromatoses (mediastinal, retroperitoneal, paraneoplastic fibrosis and desmoid tumors) after treatment with progesterone. Primary cultures of fibroblasts were prepared from fetuses of Swiss strain mice. Continuous fibroblast lines LM and Vero were also used. Moreover, cultures of non-fetal human fibroblast from skin and lung were employed. Epithelial tumor cell line HeLa was used as a control. All cultures were incubated with various doses of progesterone at concentrations from 1.4 X 10(-4) to 1.4 X 10(-3) M. Human cells and monolayers of fetal murine fibroblast were submitted to the action of medroxyprogesterone solution at the same concentrations as used for progesterone. Other steroids (estrone, estriol, testosterone and prednisolone) were used at the identical concentrations in the same vehicles. Progesterone affected all lines of fibroblasts studied and destroyed them within either 2-4 or 24-48 h depending on the steroid concentrations used. Medroxyprogesterone had a comparable effect on human cell lines and monolayers of fetal murine fibroblasts provided that the same ratio between the hormone concentration and the time of exposure was maintained. With higher medium concentrations shorter times of incubation were required for the destruction of fibroblast. However, to observe a degree of lysis similar to that elicited by progesterone, it was necessary to use 4 times higher concentrations of medroxyprogesterone. No effect on HeLa epithelial cells was observed nor were the controls affected by the steroids or diluents used at the appropriate concentrations. Results from incubation studies using monolayers of murine fibroblast and 14C-progesterone suggested that the cells were destroyed by the progesterone and not by a bioproduct of its metabolism.

Fetal and neonatal fatality in rat hybrids from mothers stimulated with parental skin.

A breeding experiment was conducted in which MAXX female rats were mated with BN male rats. These two strains of inbred rats are identical for AgB antigens and differ only in antigens governed by minor histocompatibility loci. MAXX females, which were exposed before pregnancies to four BN skin grafts, delivered 117 offspring of which 28 (23.9%) were stillborn and 10 (8.5%) dead within 24 hr of birth. In contrast, of 126 offspring in control groups, only one was stillborn and one dead within 24 hr. In BN-grafted MAXX females, placentas were partially necrotic with marked polymorphonuclear reaction, which could account for stillbirths or the newborn deaths shortly after birth. The stillborn fetuses had grossly noticeable wrinkled skin. Histologically, the architecture of the epidermis was disturbed. The dermis was edematous and contained occasional mononuclear cells.