BACKGROUND It has been known for more than 20 years that estrogen replacement therapy substantially increases a woman's risk of developing endometrial cancer. To reduce this increased risk, progestins have been added to estrogen replacement therapy for between 5 and 15 days (usually 7 or 10 days) per "month" in a sequential fashion (sequential estrogen-progestin replacement therapy) or with eac...

Our recent studies show that progestins induce vascular endothelial growth factor (VEGF) in breast cancer cells that express mutant p53 protein. Here, we show that natural and synthetic progestins also induce thrombospondin-1 (TSP-1) mRNA and protein in T47-D and BT-474 breast cancer cells. Antiprogestin RU-486 inhibits the induction of VEGF and TSP-1 by progestins, suggesting that this effect ...

Progestin-only contraceptives are associated with menstrual bleeding disturbances; a major reason why these agents are discontinued. The pathogenesis of abnormal uterine bleeding associated with progestin-only contraceptives remains ill-defined. Matrix metalloproteinases (MMPs) and leukocytes are postulated to be involved in the process of normal menstruation. Immunolocalization of MMPs and leu...

Endometria of normal histology from postmenopausal women receiving either estrogen or estrogen plus a progestin have been analyzed for nuclear estradiol receptor, epithelial DNA synthesis, isocitric dehydrogenase, and estradiol dehydrogenase activities. Epithelial DNA synthesis correlated positively with nuclear estradiol receptor and negatively with both the dehydrogenases; this result was obt...

Human progesterone receptor (PR) contains a motif that interacts with the SH3 domain of Src and mediates rapid activation of Src and downstream MAPK (Erk-1/-2) without relying on the transcriptional activity of the receptor. Here we investigated the role and intracellular location of this nontranscriptional activity of PR. Progestin activation of Src/MAPK occurred outside the nucleus with the B...

In non-human primates, the oviduct undergoes dramatic, hormonally regulated changes in morphological structure. In spayed animals, the epithelium is undifferentiated, and estro­ gen treatment can stimulate differentiation to a fully ciliated and secretory state. This state can be maintained indefinitely by estrogen, but if progestin treatment is initiated the epithelium will atrophy, dedifferen...

Women with benign proliferative breast disease are at increased risk of subsequent breast cancer. Estrogens and progesterone exert proliferative effects on mammary epithelium, and combined hormone replacement therapy has been associated with increased breast cancer risk. We tested the effect of conjugated equine estrogen plus progestin on the risk of benign proliferative breast disease in the W...

To test the hypothesis that progestin-mediated increases in resting core temperature and the core temperature threshold for sweating onset are counteracted by estrogen, we studied eight women (24 +/- 2 yr) at 27 degrees C rest, during 20 min of passive heating (35 degrees C), and during 40 min of exercise at 35 degrees C. Subjects were tested four times, during the early follicular and midlutea...

BACKGROUND In lower vertebrates, steroid-induced oocyte maturation is considered to involve membrane-bound progestin receptors. Two totally distinct classes of putative membrane-bound progestin receptors have been reported in vertebrates. A first class of receptors, now termed progesterone membrane receptor component (PGMRC; subtypes 1 and 2) has been studied since 1996 but never studied in a f...

Transrectal ultrasonography of the caudal uterus and a progestin profile were evaluated for accuracy in identifying mares with feto-placental compromise in a model of placentitis. Twenty-two pregnant ponies were divided into four groups: (1) control mares (n=5); (2) instrumented controls (n=2); (3) instrumented inoculated mares (n=11); (4) inoculated mares (n=4). Mares in Groups 3 and 4 were in...