Progesterone was administered to male rats (4 mg/day) for 10 or 13 days in two different experiments and pituitary lh stores were determined by a modified ovarian ascorbic acid depletion method. The steroid administration resulted, in both experiments, in involution of seminal vesicles and significant decreases in pituitary lh stores.
Pituitary stores of fsh and lh were determined in female rats of ages ranging from 12 to 14 days (24 g body weight) to an estimated 280 days (>375 g body weight). The aim was to study the endocrine basis for lack of ovarian compensatory hypertrophy in the aged rat. Both the concentration (μg/mg) and total content (μg/gland) of fsh in the pituitary glands of aged rats were two to three times higher than those in the glands from the adult rats (60 to 180 days old and weighing 200 to 300 g). A similar but less marked tendency was present for lh.
These results support the view that lack of ovarian compensatory hypertrophy in the aged rat is due to a decline in the output of fsh and lh from, but not due to deficiency of gonadotrophins in, the pituitary gland of the aged rat.
The luteolytic effects of prostaglandin (PG) F2α have been described in several laboratory species such as the rat (Gutknecht, Cornette & Pharriss, 1969; Labhsetwar, 1970), hamster (Labhsetwar, 1971; Gutknecht, Wyngarden & Pharriss, 1971), rabbit (Gutknecht et al., 1969) and guinea-pig (Blatchley & Donovan, 1969). This PG also induces ovulation in rats (unpublished observations) and hamsters (Labhsetwar, 1971). If the PG also exerts luteolytic and ovulation-inducing effects in the mouse, this animal might prove to be more economical for experimental purposes because of its smaller size and the limited availability of PG.
Inbred mice of ICI strain were used in this study. Adult females were exposed to males and the day when a vaginal plug was found was regarded as Day 1 of pregnancy. Crystalline PGF2α (racemic) was
Attempts were made to induce premature ovulation on the day of pro-oestrus in the 4-day cyclic rat by lh, fsh and/or prolactin administered a day earlier. Doses of 5 μg lh and 15 μg fsh, when given alone, induced partial ovulation in a few animals but the combination induced normal ovulation in 93% of the rats. Ovine prolactin given alone failed to induce ovulation and, when given in combination with lh, fsh or both, did not exert synergistic effects on ovulation. These data provide additional evidence that lh and fsh interact to induce ovulation in the normal oestrous cycle and that the ovulating hormone is composed of at least lh and fsh.
The effects of a potent antioestrogen—ICI 46,474—on cl were examined in pregnant and pseudopregnant rabbits and pregnant rats. In the rabbit, the antioestrogen interfered with the growth of cl, reducing significantly both the number and weight of the glands. In the pregnant rat, the weight of the cl was reduced and this was associated with a marked stimulation of mammary glands. These experiments provide further evidence that cl in the rabbit, and perhaps in the rat, require oestrogen for their functional maintenance.
Removal of one ovary from aged (375 g), but not from adult (200 to 250 g), rats resulted within 10 days in increased pituitary fsh stores, similar to those reached following bilateral ovariectomy. Administration of progesterone induced increased accumulation of lh and fsh in both age groups. Uteri of bilaterally spayed, aged rats formed deciduomata in response to trauma following appropriate treatment with oestrogen and progesterone.
Ovariectomy of rats on Day 3 or Day 4 of pregnancy and autopsy 5 to 6 days later, with no replacement therapy in the intervening period, resulted in an average recovery of five to six blastocysts/rat. When adrenalectomy was coupled with ovariectomy, the blastocyst recovery was markedly reduced. Administration of progesterone to such rats improved the blastocyst yield. When blastocysts from rats subjected to ovariectomy or ovariectomy and adrenalectomy were transferred to pseudopregnant hosts, the proportion which developed into viable foetuses was markedly lower than the proportion developing from blastocysts harvested from intact rats or ovariectomized rats treated with progesterone. Thus, ovariectomy alone or coupled with adrenalectomy appears to exert deleterious effects on both the number and viability of blastocysts in rats.
A possible synergistic participation of lh and fsh in the ovulatory process was explored by intravenous administration of subthreshold doses of lh and/or fsh to rats with 4-day oestrous cycles, in which ovulation was blocked by a potent anti-oestrogen—ICI 46,474. The individual gonadotrophins in the doses used were only marginally active in restoring ovulation but, when given in combination, they potentiated the incidence of ovulation in four different experiments. It is postulated that both lh and fsh synergize with each other in the induction of ovulation as they do in causing growth of follicle.
A single subcutaneous injection of progesterone (0·5 mg/animal at 17.00 hours) on Day 3 of the cycle (Day 1 = day of vaginal discharge) interfered with ovulation and external vaginal discharge in all the animals. Lower doses were only partly active. Intravenous administration of LH, FSH or their combination at 14.00 hours on Day 4 failed to restore ovulation in such animals, implying a direct action of the administered progesterone on the ovary. A large dose of oestradiol benzoate (400 μg/animal) also proved inactive suggesting that progesterone did not interfere with ovulation solely through antioestrogenic action. Depletion of the pituitary LH stores normally found in association with ovulation and the ovulatory peak of LH in plasma seen in control animals were not observed in the progesterone-treated hamsters suggesting a further action of progesterone at the pituitary-hypothalamic level in inhibiting ovulation. Administration of synthetic LRF (100 ng/animal, i.v.) on Day 4 to hamsters treated with progesterone caused an increase in plasma LH 15 min later which was comparable to the rise observed in control animals given a similar injection of LH-RF, implying lack of action of progesterone at the pituitary level. It is concluded that progesterone acts centrally, principally on the hypothalamus, and peripherally on the ovary to interfere with ovulation in hamsters. It is possible that the anovulatory state accompanying pregnancy results from these actions.
The lh content of the pituitary of rabbits in various reproductive states was assayed by the ovarian ascorbic acid depletion method. It was highest in unmated rabbits and decreased significantly (P<0·01) during both pseudopregnancy and pregnancy. Administration of progesterone (20 mg/day for 10 days) reduced pituitary lh in unmated rabbits to levels similar to those found during pseudopregnancy and pregnancy. It is inferred that the capacity of the pituitary gland to accumulate lh during pseudopregnancy and pregnancy decreases mainly as a result of secretion of progesterone.
