Uterine

Has the properties of progesterone and is given orally for treating functional uterine haemorrhage. Norethisterone, 19-norelhisterone, m.p. 20I-206°C is one of the progestational steroids used in the contraceptive pill. 

Physiological responses to prostaglandins encompass a variety of effects Some prostaglandins relax bronchial muscle others contract it Some stimulate uterine con tractions and have been used to induce therapeutic abortions PGEj dilates blood vessels and lowers blood pressure it inhibits the aggregation of platelets and offers promise as a drug to reduce the formation of blood clots... 

Two fundamental questions have emerged from these studies, ie, to what extent are agonists and antagonists binding similarly or differendy to the respective receptors, and can inhibitory compounds be developed that are active in vivo in humans as well as in vitro. An oxytocia antagonist that can block premature uterine contractions presents a promising example of the clinical utihty of such stmctures (47). Both linear as well as bicycHc modifications of these hormones also have provided new antagonist stmctures. 

In the placenta, the aminopeptidase oxytocinase, ie, cysteine aminopeptidase, is a principal catalyst for oxytocia hydrolysis and prevents premature uterine contractions. 

O. jAune and co-workers, iu M. Beato, ed.. Steroid Induced Uterine Proteins, Elsevier, Amsterdam, 1980, p. 319. 

WS-7528 [132147-69-4][VI] a nonsteroidal estrogen, is an isoflavone which has been isolated from Streptomjces sp. No. 7528 and is an estrogen agonist. It inhibits [3ff]-estradiol binding to its receptor in rat uterine cytosol at an inhibitor for 50% of the rats tested (IC q) concentration of 5.7 nM. It also induces the growth of estrogen-dependent human breast cancer cell line MCE-7 (7). 

Another structural type is chromenes. Centchroman [31477-60-8]is a pyrrolidinoethoxyplienyl chromane which is a potent antiestrogen with weak estrogenic activity. In India, it is used as a weekly contraceptive pih based on its reported abiUty to inhibit the uterine preparation for the attachment of the fertilized ova to the wall of the utems (see Contraceptives) (31). 

Estrogens stimulate cellular proliferation, induce RNA and protein synthesis of uterine endometrium and the fibrous connective tissue framework for ovaries, and increase the size of the cells. This effect leads to the growth and regeneration of the endometrial layer and spinal arterioles, and increase in the number and size of endometrial glands. Under the influence of estrogen, vaginal mucosa becomes thicker, as cervical mucus becomes thinner (85,86). 

OT receptors are localized ia the brain hypothalamus, limbic system, cortex, striatum, olfactory system, and brain stem. In the periphery, OT is best known for its stimulation of uterine smooth muscle and the milk ejection reflex. Thr , Om ]oxytocin(l—8),... 

Reproductive System. The primary PGs are intimately involved in reproductive physiology (67). PGE2 and PGP2Q, are potent contractors of the pregnant utems and intravenous infusion of either of these compounds to pregnant humans produces a dose-dependent increase in frequency and force of uterine contraction. PGI2 and TXA2 have mild relaxant and stimulatory effects, respectively, on uterine tissue. The primary PGs also play a role in parturition, ovulation, luteolysis, and lactation and have been impHcated in male infertility. 

The precise mechanism of nitrate action is not cleady understood and may be a combination of many factors. The basic pharmacologic action of nitrates is a relaxation of most vascular smooth muscle, eg, vascular, bronchial, gastrointestinal, uretal, uterine, etc. Vascular smooth muscle relaxation is a... 

Comphcations associated with lUDs include uterine perforation and pelvic inflammatory disease (95). Uterine bleeding and cramping are the most common causes for discontinuation of this method. 

After insertion of an lUD, polymorphonuclear leukocytes and macrophages accumulate in the uterine cavity. These cells appear to phagocytize sperm and Hberate a blastotoxic toxin (92,93). Intrauterine devices also may create a hostile environment, perhaps because antibodies are produced that interfere with implantation of the fertilized ovum (93). 

LNG-20, a long-lasting levonorgestrel-releasing lUD, is still under development at the Population Council. Other lUDs in development are the Multiload Mark II (marketed in Einland), the Uterine-Occluding Device, and two new copper devices, the OmbreUe and the Eincoid-350. 

In an animal study of rats exposed by inhalation to ethylene oxide at 10, 33, or 100 ppm for approximately two years (245), and in a separate chronic rat study in which rats were exposed to 50 or 100 ppm of ethylene oxide (240), increased incidences of mononuclear cell leukemia, peritoneal mesothelioma, and various brain tumors have been reported. In an NTP (246) two-year inhalation study of mice at 50 and 100 ppm, alveolar/bronchiolar carcinomas and adenomas, papillary cystadenomas of the harderian gland, and malignant lymphomas, uterine adenocarcinomas, and mammary gland tumors were increased in one or both exposure groups. 

Uracil is used more effectively, in nucleic acid synthesis within a rat hepatoma than in normal liver. This observation appears to have stimulated the synthesis of 5-fluorouracil (1027) as an antimetabolite mainly because the introduction of a fluorine atom involves a minimal increase in size. In the event, 5-fluorouracil did prove to have antineoplastic activity and it is now a valuable drug for treatment of tumors of the breast, colon or rectum, and to a lesser extent, gastric, hepatic, pancreatic, uterine, ovarian and bladder carcinomas. As with other drugs which interfere with DNA synthesis, the therapeutic index is quite low and great care is required during treatment (69MI21301). 

Rodent 3-day uterotrophic assay increase in uterine weight in ovariectomised rat. 

---