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The guinea-pig has an oestrous cycle of 16 to 18 days. Many original observations in reproductive endocrinology such as formation of deciduoma in response to trauma (Loeb, 1907), existence of the oestrous cycle (Stockard & Papanicolaou, 1917) and the ability of the uterus to modify luteal function (Loeb, 1923) involved the guinea-pig as the experimental animal. Several studies have delineated the pattern of progesterone secretion during the oestrous cycle of guinea-pigs (Heap, Perry & Rowlands, 1967; Feder, Resko & Goy, 1968; Challis, Heap & Illingworth, 1971; Blatchley, Donovan, Horton & Poyser, 1972) but comparative changes in the secretion of oestrogens have received very little attention. Challis et al. (1971) attempted to measure total oestrogens by radioimmunoassay in the peripheral plasma, but failed to detect any due to their very low levels. In the present study, we determined

The role of oestradiol in the control of uterine responsiveness to oxytocin was investigated by measuring oxytocin-induced phospholipase C activation in [³H]inositol-labelled cultured human myometrial cells. Addition of oestradiol to steroid-free culture medium (10% (v/v) fetal calf serum treated with dextran-coated charcoal in phenol red-free medium) enhanced formation of inositol phosphates and this effect was completely abolished by the anti-oestrogen tamoxifen. The inhibitory effect of tamoxifen on oxytocin-induced phospholipase C activation occurred in both steroid-free and complete culture medium; it was time- and concentration-dependent and was only partly reversed by oestradiol. When phospholipase C was activated with PGF_2α or fluoroaluminate instead of oxytocin, oestradiol and tamoxifen had the same stimulatory and inhibitory effects, respectively. The inhibitory effect of tamoxifen could not be prevented by treating the cells with pertussis toxin. Moreover, the effect of tamoxifen was not mediated by inhibition of protein kinase C, since the use of staurosporine (a protein kinase inhibitor) resulted in potentiation of phospholipase C activation by oxytocin. Both oestradiol and tamoxifen increased [³H]inositol incorporation into cellular lipids and cell proliferation. These results suggest that oestradiol enhances myometrial responsiveness to oxytocin and other agonists by facilitating phospholipase C activation at a post-receptor level. This effect is antagonized by tamoxifen; however, tamoxifen also has oestrogen-independent inhibitory effects.

Summary. Glandular epithelial and stromal cells were isolated from the endometrium of mares by collagenase digestion and were incubated on plastic for 7–9 days until the cells formed confluent monolayers. The cells differed in morphology: epithelial cells appeared polyhedral and stromal cells were spindle like. The monolayers were incubated in the presence and absence of oxytocin. Medium was removed from wells after 2, 8 and 24 h of incubation. Concentrations of prostaglandin F (PGF) in the medium increased significantly during this time. Glandular epithelial cells produced significantly more PGF than did stromal cells. Both types of cell responded significantly to oxytocin stimulation by increased secretion of PGF; the response of glandular epithelial cells tended to be greater than that of stromal cells. Secretion of PGF by cultured cells was not affected by cycle stage or pregnancy.

Keywords: endometrium; cell culture; prostaglandins; horse