William T. K. Bosu

The effect of various dosages of lynestrenol on the plasma levels of oestrogens and progesterone during the menstrual cycle in the rhesus monkey

Abstract The effect of daily oral doses of lynestrenol on the ovarian function was investigated in nineteen rhesus monkeys. The compound was given in four dose levels 0.05, 0.25, 1 and 2.5 mg daily throughout the menstrual cycle. Plasma samples collected before during and after treatment were analysed for their content of estrogen and progesterone. The low doses 0.05 and 0.25 had no effect on the occurrence of ovulation, the plasma levels of the ovarian steroids being similar to those seen during normal ovulatory cycles. Lynestrenol treatment at doses of 1 and 2.5 mg per day prevented ovulation. The estrogen levels in monkeys treated with 1 mg lynestrenol appeared normal, but the progesterone levels were never more than 0.4 ng/ml. In the monkeys treated with 2.5 mg lynestrenol the estrogen levels were below the lowest levels of the control cycles and the progesterone levels were less than 0.2 ng/ml. The female rhesus monkey appears to require about ten times more lynestrenol per kg body weight than women for suppression of ovulation. However, the plasma levels of norethindrone, which is the active metabolite of lynestrenol, required for ovulation inhibition does not appear to be grossly different from those found in women.

Ovarian steroid patterns in peripheral plasma during the menstrual cycle in the rhesus monkey.

The plasma patterns of oestrogens, progesterone and 17α-hydroxyprogesterone were studied during 18 normal menstrual cycles in 15 rhesus monkeys. Radioimmunoassays and competitive protein binding were used for the determination of the plasma levels of the steroids. The average patterns of the steroids in plasma and their relation to ovulation, menstruation and normality of the cycles studied are described.

Effects of postovulatory norethindrone and estrogens on the plasma levels of estrogen and progesterone in Rhesus monkeys

Abstract Norethindrone, ethinylestradiol and diethylstilbestrol were administered during the luteal phase in 31 menstrual cycles in rhesus monkeys. In eight of these cycles, chorionic gonadotrophin was administered when treatment with the compounds was discontinued. The effects of the compounds on the estrogen levels in plasma were insignificant. During treatment with norethindrone, progesterone levels decreased. A slight increase after treatment occurred in some cycles. Treatment with diethylstilbestrol resulted in an initial depression followed by an increase of plasma progesterone levels. The progesterone levels either increased or remained unchanged during and after ethinylestradiol treatment. Chorionic gonadotrophin administration after treatment with the compounds resulted in rapid surges of both progesterone and estrogen levels in the monkeys treated with the estrogens, but not in the monkeys treated with norethindrone.

The Function of the Corpus Luteum in Primates

The corpus luteum in nonpregnant primates secretes progesterone and estrogens for a limited period of 14 days. In many lower animals, the uterus determines the life span of the corpus luteum (Anderson et al., 1969). The corpus luteum in women and rhesus monkeys will function during its full life span even if the uterus is removed (Beling et al., 1970; Neill et al., 1969). In the primate, the implanted blastocyst rapidly produces chorion gonadotropins that stimulate the dying corpus luteum to continue to produce progesterone and estrogens until the placenta is capable of taking over the function.

IMPLANTATION AND MAINTENANCE OF PREGNANCY IN MATED RHESUS MONKEYS FOLLOWING BILATERAL OOPHORECTOMY OR LUTEECTOMY WITH AND WITHOUT PROGESTERONE REPLACEMENT

Six mated rhesus monkeys were bilaterally oophorectomized between the fourth and sixth day after ovulation, and received silastic implants containing crystalline progesterone subcutaneously. Five mated monkeys were subjected to luteectomy 5 or 6 days after ovulation. Three of these received progesterone implants subcutaneously. Pregnancy occurred in one oophorectomised monkey and in all three luteectomised monkeys treated with progesterone. It was evident from the steroid patterns observed in the pregnant monkeys that the ovarian tissue other than the corpus luteum contributes to part of the oestrogen seen around the time of implantation. The corpus luteum apears to be the main source of progesterone in the peripheral plasma during this period. Placental progesterone production in early pregnant rhesus monkeys starts at three weeks after ovulation and the placental production of progesterone precedes that of oestrogen.