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The effect of different progestogens on the properties of the uterine fluid of ligated, oestradiol-primed spayed rats were studied.The substances investigated were: pregnane derivatives: chlormadinone acetate, medroxyprogesterone acetate, dydrogesterone, and 19-nortestosterone derivatives: norethisterone acetate, norethynodrel, d1-norgestrel and lynestrenol, and their effect on uterine fluid volume and viscosity were studied.Whereas pregnane derivatives display progesterone like effects (decrease of fluid volume, increased viscosity)following both parenteral and oral administration, the effects of the 19-nostestosterone derivatives differ in some respects from those of the progesterone derivatives.Norethisterone and d1-norgestrel which still contain the 3-keto group and a double bond in 4 positions exert progesterone-like effects in low parenteral (s.c.) doses. A slight effect only being observed in response to 100 times higher oral doses.Norethynodrel and lynestrenol in which the ring A is modified exhibited no progesterone-like activity by either the subcutaneous or the oral route. Specific differences in sensitivity and in metabolic pathways can be traced as possible origin of the results obtained.

Ovariectomized adult rats with closed uteri were treated for 7 days with different oral and s..c. doses of oestradiol, oestrone, oestriol and ethinyl oestradiol. All treatments elicited the production of uterine fluid and the potencies of oestrogens were related to the amount of fluid secreted. Ethinyl oestradiol and oestradiol displayed similar activity when given s.c. A daily dose of 0-003 mg oestradiol/kg resulted in about 700 mg fluid. Oestrone was 3-10 times and oestriol about 100 times less active. Orally, ethinyl oestradiol was the most potent substance and 700 mg secretion was obtained with a dose of 0-03 mg/kg daily. Oestradiol was about 30 times, oestrone about 100 times and oestriol 50 times less active than ethinyl oestradiol by this route. The viscosity of the secretion was unaffected, remaining between 1-6 and 2-4 cP. The pH of the fluid did not change, but that of the uterine lumen diminished slightly. These effects of oestrogens were associated with an increase in the weight of the empty uterus and a decrease in body weight.

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It was found that closure of the uterus disturbed the first 2 cycles after the operation; thereafter the normal cycle was resumed. The quantity of uterine fluid was increased at pro-oestrus and oestrus and reduced at met-oestrus and di-oestrus. Slight inverse changes in viscosity were observed. There was no significant difference in the pH. The corona-cell dispersing factor seems to be an oestrogen-dependent constituent of uterine secretion.

In oestradiol-primed, spayed rats, the uterinesecretion was allowed to accumulate for 21 days after ligaturein rats of the uterus. From the 14th to the 21st day, the followingsubstances were administered in varying subcutaneous doses(1) chlormadinone acetate; (2) medroxyprogesterone acetate;(3) dydrogesterone; (4) norethisterone acetate; (5) d, 1-norgestrel; (6) lynestrenol; (7) nor-ethynodrel. One solvent-treated group served as controls. Ova were removed from the oviducts of normal rats in oestrus, placed separately in small closed chambers containing uterine fluid recovered from the treated animals, and incubated for 6 h at 37 °C. The surface projection (100 ×) of the egg and its corona cells was measured planimetrically.After incubation in uterine secretion from control rats, the surface area increased (about 2.4 times), owing to dispersion of the entire corona. The uterine secretion of rats pretreated with substances 1 to 5 inhibited dispersion proportionately to the dose administered, whereas substances 6 and 7 were without effect.These results are discussed in connection with previous observations on the quantity, viscosity and pH changes in the uterine fluid of rats pretreated with the same steroids.