Progesterone synthesis in developing rabbit corpora lutea in the absence of follicular estrogens.

We have investigated the role of 17beta-estradiol in the early development of the rabbit corpus luteum. Ectopic corpora lutea were established in all animals by autotransplanting preovulatory follicles beneath the kidney capsule 6.5 to 8 h after mating (day 0). At this time, the rabbits were bilaterally ovariectomized and in some of these rabbits a Silastic capsule containing crystalline 17beta-estradiol was implanted SC. Mean serum concentration of estradiol in rabbits with an estradiol impant was 16.4 pg/ml. In rabbits without an estradiol implant, the estradiol concentration averaged 1 pg/ml despite the presence of transplanted luteinized follicles. Daily blood samples were analyzed for progesterone by radioimmunoassay. Ectopic corpora lutea developed in rabbits with or without estradiol treatment. Serum progesterone concentrations in the two groups increased above castrate values and were not significantly different from one another through day 5. After day 5, progesterone concentrations steadily increased in rabbits treated with estradiol and reached a value of 4.8 ng/ml by day 10. In contrast serum progesterone steadily decreased after day 5 in rabbits without estradiol treatment to a level of 450 pg/ml by day 10. Hysterectomy on day 0 did not prevent this decline in progesterone, indicating that a uterine luteolytic agent was not involved. Total luteal weight on day 10 was positively correlated with serum progesterone concentration (r equals .92; P greater than 0.01). These results indicate that for a period of approximately 5 days afte r ovulation, the development of the rabbit ectopic corpus luteum and the secretion of progesterone are autonomous from estradiol secreted by ovarian follicles. After this time, there is an absolute requirement for estrogen which permits further development of the corpus luteum and the continuation of progesterone synthesis.     

Estradiol-17 beta secretion by the newly formed corpus luteum of a macropodid marsupial, the quokka (Setonix brachyurus).

The production of significant amounts of estradiol-17 beta from the 2-day-old corpus luteum of the macropodid marsupial, Setonix brachyurus (quokka), was shown using an in vitro perifusion system. Sliced corpora lutea and finely chopped extra-luteal ovarian tissue (cortex plus interstitial tissue) were perifused separately for 2 hr, in tandem for the next hour (with the perifusate from the ovarian tissue directed into the chamber containing the corpora lutea), and separately again for a further 2 hr. Overall production rates of estradiol measured by radioimmunoassay were 1.0 pg (mg hr)-1 from luteal tissue and 0.64 pg (mg hr)-1 from the extra-luteal tissue. Androgen production rates were 0.18 ng (mg hr)-1 and 0.06 ng (mg hr)-1 from luteal and extra-luteal tissues, respectively, and progesterone was produced at a rate of 0.80 ng (mg hr)-1 from luteal tissue and 16.5 pg (mg hr)-1 from extra-luteal tissue. Production rates of all three steroids from the perifused tissue increased significantly when the ovary and corpus luteum were perfused in tandem. The secretion of C19 and C18 steroids from the young corpus luteum suggests that luteinization is not yet complete at this stage in the reproductive cycle of the quokka, and the tissue would be better described as a "postovulatory follicle." This is supported in the literature by the occurrence of mitoses in granulosa cells for 6-7 days after resumption of the delayed cycle. This delayed maturation of the macropodid corpus luteum, which is associated with the secretion of significant quantities of estradiol and only a transient spike of progesterone, is discussed in relation to the longer cycles and gestation periods characteristic of macropodid marsupials.     

Morphological and endocrine correlates of the reproductive cycle of the aplacental viviparous dogfish, Squalus acanthias

Pregnant female spiny dogfish were captured off the coasts of Maine and Massachusetts and morphometric and gravimetric analyses of the liver, gonad, and reproductive tract correlated with the reproductive cycle. Plasma samples were taken and circulating steroids (progesterone, testosterone, and estradiol) were measured by radioimmunoassay. Clear-cut temporal variations in plasma steroid levels were observed, which correlated with the ovarian cycle. Testosterone and estradiol-17 beta levels were low (100-200 pg/ml plasma) in early pregnancy when ovarian follicles were small but increased to about 10 ng/ml as follicles grew and gestation progressed. By contrast, plasma progesterone was high (2-6 ng/ml) in early to mid-pregnancy when corpora lutea were active and declined toward term (less than 1.0 ng/ml).     

Ovarian steroid metabolism and oestrogens in the corpus luteum of the tammar wallaby

Ovaries were obtained from tammar wallabies at various stages of the reproductive cycle to examine the occurrence of oestrogens in corpora lutea, and the synthesis and metabolism of steroids in the corpus luteum and ovarian cortical and interstitial tissues. Corpora lutea contained oestradiol-17 beta and oestrone during embryonic diapause and at all stages of pregnancy studied after blastocyst activation. Aryl sulphatase, 3 beta-hydroxysteroid dehydrogenase and 17 beta-oxidoreductase were shown to be present in luteal and other ovarian tissues by incubation in vitro with labelled substrates. Aromatase was undetectable in corpora lutea or in interstitial tissue, but was present in the ovarian tissues (including follicles) which remained after removal of corpora lutea. The probable source of the oestrogens detected in the corpus luteum is discussed in relation to their role in the inhibition of follicular development during embyronic diapause.     

The control of progesterone secretion during the estrous cycle and early pseudopregnancy in the rat: prolactin, gonadotropin and steroid levels associated with rescue of the corpus luteum of pseudopregnancy.

The hormonal factors associated with converting a corpus luteum of estrous cycle into a corpus luteum of pseudopregnancy were studied by measuring LH and FSH prolactin, estradiol and progesterone levels in decapitated rats during the 4-day estrous cycle and a comparable time of pseudopregnancy (lights on 0600-0800 hr.). During the estrous cycle, prolactin, LH and FSH remained low and unchanging except on the afternoon of proestrus, when typical proestrous surges were observed. In contrast, estradiol levels began to increase on D-1, from baseline values of 7 pg/ml to approximately 15-20 pg/ml. These levels were maintained until the afternoon of D-2 when estradiol further increased to reach peak levels of 40-50 pg/ml by 0900 hr on proestrus. Estradiol then declined in relation to the increase in LH secreation and had returned to baseline by estrus. Progesterone secretion by the corpora lutea of the cycle also increased on the afternoon of D-1 and reached a maximum value of 25-30 ng/ml early on the morning of D-2. At this time, a precipitious fall in progesterone occurred, returning to baseline values of 5-1- ng/ml by 0700 on D-2 signifying the regression of the corpora lutea of the cycle. Progesterone remained low thereafter until the afternoon of proestrus when levels increased in response to the proestrus when levels increased in response to the proestrous surge of LH. Following cervical stimulation at 1900 hr on proestrus, no differences were noted, with respect to the estrous cycle, in LH, FSH or estradiol secreation through the afternoon of D-2. Surprisingly, progesterone levels did not differ in the cycle and pseudopregnancy until the early morning of D-29 instead of progesterone levels falling to baseline as they had during the cycle, the corpora lutea of pseudopregnancy were rescused, progesterone increasing dramatically to reach levels of 45-50 ng/ml by 1700 hr on that same day. The only difference in hormone secretion that was noted which could account for this marked divergence in progesterone secretion was the pattern of prolactin secretion following cervical stimulation. In contrast to the low levels seen during the estrous cycle, biphasio surges of prolactin secretion occured each day, one being nocturnal (0100-0900 hr) and the other diurnal (1500-2100 hr). The rescue of the corpus luteum occured in association with the nocturnal surge on D-2. These results suggest that nocturnal surge on D-2, PROLACTIN IS THE MAJOR Luteotropic stimulus which transforms and estrous cycle into pseudopregnancy by prolonging progesterone secretion from the corpus luteum. Moreover, if LH is important for progesterone secretion, no changes were observed in the pattern of LH secretion which can account for the rescue of the corpus luteum.     

Immunocytochemical localization of estradiol and progesterone receptors in the monkey ovary throughout the menstrual cycle

Both estradiol and progesterone may act locally to modulate ovarian function in various species. This study examined the distribution of estradiol and progesterone receptors (ER and PR, respectively) within the primate ovary throughout the menstrual cycle. Ovaries were collected from rhesus or cynomolgus monkeys during the early, mid-, and late (n = 3-6/stage) follicular and luteal phases of the cycle. The tissues were processed for indirect immunocytochemical localization of receptors with specific monoclonal antibodies against ER (H222 and D75) and PR (JZB39). Specific immunocytochemical staining, as determined by comparing adjacent tissue sections incubated with either receptor antibodies or a nonspecific antibody, was exclusively nuclear. Both ER and PR were localized in the germinal epithelium of ovaries at all stages of the cycle. ER was not detected in any other ovarian structure (i.e. stroma, follicles, interstitial tissue, or corpora lutea) regardless of the stage of development. However, ER was detected in other estrogen-responsive tissues, e.g. the oviduct of the monkey and corpora lutea of the pseudopregnant rabbit. In the monkey ovary, PR was detected in stromal and interstitial tissues as well as theca interna and externa of healthy and atretic follicles at all stages of the cycle. The granulosa cells of some primordial and primary follicles demonstrated staining for PR. However, the granulosa layer of follicles that developed beyond the primary stage were consistently negative for PR. Only the granulosa layer of large preovulatory follicles that showed signs of luteinization after the LH surge showed staining for PR equivalent to that in the theca. Monkey corpora lutea exhibited specific nuclear staining for PR. Moreover, the percentage of receptor-positive nuclei in the corpus luteum varied (P less than 0.05) between the early (28 +/- 3%), mid (48 +/- 1%)-, and late (4 +/- 2%) luteal phase of the cycle. Nonfunctional (serum progesterone less than 0.5 ng/ml) regressing corpora lutea did not exhibit for staining for PR. Luteal cells that were PR positive also contained histochemically detectable 3 beta-hydroxysteroid dehydrogenase. These data are consistent with the concept of a receptor-mediated autocrine or paracrine role for progestins, but not estrogens in the gametogenic and endocrine functions of the primate ovary throughout the menstrual cycle.     

Immunocytochemical demonstration of oxytocin in bovine ovarian tissues

The presence of oxytocin in ovarian tissue was examined immunocytochemically. Bovine antral follicles and corpora lutea were fixed with glutaraldehyde, picric acid and acetic acid fixative and immuno-stained by the indirect peroxidase-antiperoxidase (PAP) technique. Immunoreactive oxytocin was demonstrated in the granulosa cells of small and large follicles, in the granulosa-lutein cells of the young corpus luteum and in the large luteal cells of the mature corpus luteum. The regressing corpus luteum was not stainable. It is discussed that these findings additionally support the view that oxytocin is actually synthesized in ovarian tissues.     

Ovarian features of the wild collared peccary (Tayassu tajacu) from the northeastern Peruvian Amazon

In this study, the ovaries of 27 wild collared peccaries (Tayassu tajacu) from the Amazonian region of northeastern Peru were examined macroscopically and microscopically, and expression of major steroidogenic enzymes was detected by immunohistochemistry. Our observations suggest a mean ovulation rate of 2.3 +/- 0.6 follicles and a low rate of reproductive wastage (0.4 +/- 0.6 oocytes or embryos per pregnancy). The collared peccary seems to exhibit follicular waves involving the synchronous growth of a cohort of follicles, several of which seem to attain selection. The presence of antral follicles in pregnant females suggests that follicular turnover continues during pregnancy. In cyclic animals, corpora lutea were characterised by the presence of distinct large and small luteal cell populations. The luteal volume in pregnant females was larger than that recorded for non-pregnant females. Through immunohistochemistry, it was observed that luteal cells from active corpora lutea exhibit intensive 3beta-HSD expression in advanced stages of pregnancy. This suggests that the corpora lutea seems to remain steroidogenically active throughout pregnancy and likely contribute to progesterone production during pregnancy.     

Mesotocin and luteal function in macropodid marsupials

Pituitary glands and corpora lutea collected at various stages of the reproductive cycle of the tammar wallaby (Macropus eugenii), were extracted and fractionated by high-performance liquid chromatography, and specific radioimmunoassays were used to measure mesotocin ([Ile8]-oxytocin) and oxytocin. Mesotocin, but not oxytocin, was identified in extracts of pituitary; the mean concentration of mesotocin in this tissue was 0.75 nmol/g wet weight. Neither mesotocin nor oxytocin was detected in extracts of corpus luteum. In female Bennett's wallabies passively immunized against mesotocin during seasonal reproductive quiescence, there was no significant effect on peripheral progesterone concentrations and there were no births, matings or changes in vaginal smears in the 2 months following treatment. Thus mesotocin is unlikely to act as a systemic luteostatic agent during seasonal quiescence.     

Estrogen regulation of steroidogenesis in rabbit luteal cells

Estradiol is a potent modifier of gonadotropin-stimulated steroidogenesis. By the seventh day after ovulation, estradiol is the only agent required for the stimulation of progesterone synthesis by corpora lutea of superovulated pseudo-pregnant rabbits. To learn which control points in steroidogenesis are susceptible to regulation by estradiol alone, we have studied the production of pregnenolone, progesterone, and 20 alpha-hydroxy-4-pregnen-3-one by corpora lutea of estradiol-stimulated and estradiol-deprived pseudopregnant rabbits. In previous investigations, we learned that estradiol deprivation in vivo, on day 9 of pseudopregnancy, causes an abrupt cessation of progesterone and 20 alpha-hydroxy-4-pregnen-3-one production, which is associated with accumulation of cholesterol and cholesteryl ester in the luteal tissue. We now report that production of pregnenolone, measured as its concentration in serum, also decreases abruptly by 84% within 48 h when the estradiol stimulus is removed on day 9 of pseudopregnancy. In addition, short term incubations of luteal tissue demonstrate that corpora lutea from estradiol-deprived rabbits do not use stores of luteal intracellular cholesterol for production of pregnenolone and progestin. These findings suggest that upon estradiol deprivation, rabbit luteal cells lose their capacity for using stored cholesteryl ester, or cholesterol synthesized de novo, for the production of pregnenolone and progestins. We, therefore, tested the hypothesis that a blockade of steroidogenesis caused by estrogen deprivation occurs at the point of cytochrome P-450 cholesterol side-chain cleavage (P-450scc), a principal rate-limiting step in the conversion of cholesterol to hormonal steroid products. To this end, we assayed the P-450scc activity in mitochondria-rich fractions of corpora lutea from rabbits that were deprived of estradiol for 24 and 48 h beginning on day 9 after induction of superovulation. Surprisingly, withdrawal of the estradiol stimulus did not cause loss of luteal P-450scc activity, measured as the amount of aminoglutethimide-inhibitable conversion of 25-hydroxycholesterol to pregnenolone by mitochondria-rich preparations. From these results, we infer that the luteotropic action of estradiol is probably not effected at P-450scc in the rabbit corpus luteum, but, presumably, occurs at control points that regulate the availability of stored cholesterol and/or its movement to or within the mitochondria for conversion to pregnenolone.     

Allopregnanolone and pregnanolone are produced by the human corpus luteum

Using a dispersed human luteal cell culture model, progesterone, allopregnanolone and pregnanolone release following treatment by incremental doses of human chorionic gonadotrophin (hCG) were evaluated. Corpus luteum tissues, obtained from 48 healthy women scheduled for benign surgery, were grouped according to luteal age and tissue concentration of allopregnanolone and pregnanolone was determined. The mRNA expression of 5alpha-, and 5beta-reductase and 3alpha-HSOR mRNA expressions were evaluated in corpora lutea from the late luteal phase. Allopregnanolone concentrations in corpus luteum tissue were consistently about three- to four-fold higher than pregnanolone levels. Allopregnanolone tissue concentrations significantly decreased between early- and late-luteal phase, p<0.05. When exposed to hCG, progesterone output from freshly obtained human corpora lutea cells was two- three-fold increased compared to control levels. With 0.1U/ml hCG a two-fold increase in allopregnanolone levels were noted, whereas pregnanolone levels were increased by approximately 40%. Furthermore, the mRNA of 5alpha-, 5beta-reductase and 3alpha-HSOR mRNA were all expressed in human corpus luteum. In conclusion, the neurosteroids allopregnanolone and pregnanolone are produced in the human corpus luteum and their release is stimulated by trophic hormone.     

Ontogenesis, distribution and relative sensitivity of hCG receptors to hCG and LH in goat ovaries.

The binding of [125I]hCG to immature and mature follicles and corpora lutea of goat ovaries has been studied. The hormone is bound maximally by corpora lutea although mature follicles also exhibit some binding. Immature follicles are practically devoid of receptors for this hormone. In the corpus luteum, the receptors for the hormone are present in thecal and luteal cells. Autoradiographic studies show the location of the bound radioactivity grains primarily along the plasma membranes of these cells, although some radioactivity grains were also seen in the cytoplasm of luteal but not thecal cells. On a mole to mole basis, hCG was found to displace [125I]hCG from binding to receptors on corpus luteum better than hLH and oLH.     

The role of the corpus luteum of lactation in the bandicoot Isoodon macrourus (Marsupialia: Peramelidae)

The concentration of progesterone in the plasma of the bandicoot was determined during pregnancy, during lactation, following removal of the young, and following surgical removal of the corpora lutea of lactation alone or along with the removal of the young. The corpus luteum of pregnancy continued into lactation and secreted progesterone for the first 19 days of lactation. In the later stages of lactation, the corpus luteum, which persisted morphologically until Day 45, was not secretory. Ovulation occurred approximately 20 days after the removal of the pouch young early in lactation. However after removal of both young and corpora lutea ovulation occurred in approximately 10 days. Thus early in lactation, when it is secreting progesterone, the corpus luteum may exert an additional ovulation inhibitory effect over and above that provided by suckling, but at later stages of lactation it is the suckling stimulus which is all important in inhibiting ovulation.     

The persistence of the corpus luteum of pregnancy into lactation in the marsupial bandicoot, Isoodon macrourus

The bandicoot is unique among marsupials in possessing a corpus luteum of pregnancy which continues to secrete progesterone during lactation. Different factors which may influence the activity of this corpus luteum were examined. There was no correlation between the number of pouch young and the plasma progesterone concentration. Similarly, bromocriptine did not appear to cause a dramatic decrease in plasma progesterone early in lactation, however, it may induce premature regression of the corpus luteum late in lactation. Corpora lutea were not observed in the ovaries of two out of six bandicoots treated with bromocriptine late in lactation. Although the corpus luteum may influence ovarian activity early in lactation, and corpus luteum does not appear to influence reproduction late in lactation. Removal of corpora lutea at Day 30 of lactation caused an abrupt decline in plasma progesterone; however, the birth of the subsequent litter occurred on Days 58 and 61 (N = 2), births normally occurring on Day 60.     

Steroid levels in preovulatory and gravid lizards (Uromastix hardwicki)

Progesterone, testosterone, and estradiol-17β were measured by radioimmunoassay in the plasma and ovarian tissues of preovulatory and gravid spiny-tailed lizards (Uromastix hardwicki). Plasma titers of all three steroids were significantly higher in females carrying the oviductal eggs as compared to the values obtained in the preovulatory animals. Progesterone content of the corpora lutea present in the ovaries of gravid females was several times higher than the concentration of this hormone in the preovulatory follicular tissue. Testosterone and estradiol concentrations were also significantly higher in the luteal than in the follicular tissues. These data suggest that the rise in plasma levels of steroids during gravidity is mainly due to the steroidogenic activity of the corpus luteum and that the functions generally attributed to the reptilian luteal tissue may be mediated not only by progestins alone but also by other steroids synthesized by the corpus luteum in this reproductive phase.     

Prolactin stimulates steroidogenesis by human luteal tissue in vitro

Human luteal tissue recovered from varying stages of the luteal phase was minced and incubated for 3 h and the effect of human chorionic gonadotrophin (hCG), prolactin and hCG + prolactin on progesterone and oestradiol production measured. While hCG generally enhanced both progesterone and oestradiol synthesis, prolactin alone at either 20 or 200 micrograms/l had no significant effect on steroidogenesis. When prolactin was added along with hCG in four of six corpora lutea, however, progesterone production significantly increased and in three of six corpora lutea oestradiol production was increased above that induced by hCG alone. It is concluded that prolactin may play some role in the control of steroidogenesis by the human corpus luteum.     

Premature regression of corpora lutea in pseudopregnant rabbits following the removal of polydimethylsiloxane capsules containing 17 beta-estradiol.

17-beta-Estradiol, which is luteotropic in rabbits, was administered during pseudopregnancy via polydimethylsiloxane (Silastic) implants to determine the effects on serum progesterone concentrations. Implants which released estradiol at a rate of approximately 2 mug/day were place beneath the skin the day after sterile mating and ovulation (day 0). Blood (3 ml) was obtained from the marginal ear vein on days 3, 6, 9, 10, 11 and 12. Serum estradiol levels, determined by radioimmunoassay, were 2- to 3-fold higher in estradiol-treated rabbits (11.7 plus or minus 1.2 pg/ml) than in untreated pseudopregnant controls (5.9 plus or minus 1.4 pg/ml). Weights of corpora lutea in treated and control rabbits were not different at the conclusion of the experiment on day 12. Serum progesterone concentrations, also determined by radioimmunoassay, were not significantly different between treated and control animals. However, when estradiol implants were removed from other rabbits on day 10, a rapid decline in serum progesterone occurred, from 14.0 plus or minus 2.4 to 2.6 plus or minus 0.8 ng/ml 24 h later. By comparison, serum progesterone concentrations in rabbits with estradiol implants left in place and in untreated rabbits on day 12 were similar (similar to 12 ng/ml). The premature decline in serum progesterone was accompanied by a decrease in the wet weight of corpora lutea. Other experiments revealed: 1) a precipitous fall in serum estradiol to basal values within 2 h after estradiol implants were removed, preceding the decline in serum progesterone by approximately 6 to 10 h; 2) reduced levels of estradiol in ovarian venous blood, but elevated levels of estradiol in peripheral arterial blood of rabbits with estradiol impants. The inability to elevated estradiol to increase serum progesterone or weights of corpora litea suggests that the luteotropic effect is maximal when estradiol is present at physiological concentrations. Following the continuous administration of estradiol, ovarian secretion of estradiol appears diminished and the corpora lutea become dependent upon the exogenous estradiol for luteotropic support. Although the ovaries continue to release measureable quantities of estradiol, this is inmeasurable quantities of estradiol, this is insufficient to prevent regression of corpora lutea when exogenous estradiol is rapidly withdrawn from the circulation.     

Estradiol suppression of luteinizing hormone (LH)/human chorionic gonadotropin receptors and LH-sensitive adenylyl cyclase without decreased adenosine 3',5'-monophosphate content in rabbit corpora lutea

It has been observed that elevated concentrations of estradiol, the principle luteotropin in the rabbit, reduce LH-stimulated adenylyl cyclase activity in corpora lutea during midpseudopregnancy without suppressing serum and tissue progesterone concentrations. If LH modulates intraluteal cAMP levels in this species, this suggests that in the presence of exogenous estradiol, progesterone synthesis may be independent of cAMP. To test this possibility and to investigate the physiological significance of LH in regulating the rabbit corpus luteum, the concentrations of cAMP and progesterone and the activity of adenylyl cyclase were measured in luteal homogenates, the numbers of LH/hCG receptors were estimated in crude membrane preparations, and the concentrations of progesterone and estradiol were measured in serum on days 2-12 of pseudopregnancy in rabbits treated with or without estradiol. Throughout days 2-12 of pseudopregnancy, estradiol treatment increased LH-stimulated adenylyl cyclase activity on day 2, but reduced its activity after day 4 by up to 50%, reduced the number of LH/hCG receptors after day 2 by up to 50%, and had no effect on the activities of basal, epinephrine-stimulated, or NaF-stimulated adenylyl cyclase. Tissue cAMP levels were not altered by estradiol treatment, nor were serum progesterone concentrations (except for an increase on day 2). Since LH receptors and LH-stimulated adenylyl cyclase were both reduced by day 5 of pseudopregnancy without a concomitant decrease in luteal cAMP or serum progesterone concentrations, our data suggest that LH is not a physiological regulator of luteal cAMP or serum progesterone during days 4-12 of pseudopregnancy. We propose that basal adenylyl cyclase activity, which is not reduced by estradiol treatment, may play a more significant role than LH-stimulated adenylyl cyclase activity in regulating tissue cAMP levels and the progesterone synthetic capacity of the rabbit corpus luteum.     

Control of corpus luteum function in the pregnant rabbit: role of estrogen and lack of a direct luteotropic role of the placenta

The corpus luteum is essential for pregnancy maintenance in the rabbit and appears to require two luteotropins: estrogen from ovarian follicles and a placental luteotropic factor. We have investigated the role of the placental luteotropic factor in maintaining corpus luteum function in the pregnant rabbit in the absence of estrogen. In Exp 1, follicular estrogen was withdrawn on day 21 of pregnancy by ovulating follicles with 10 IU hCG. In Exp 2, estrogen was withdrawn in hypophysectomized pregnant rabbits on day 21 by removing an estradiol (E2) implant. In the presence of this estrogen implant, luteal function and pregnancy are maintained after hypophysectomy, performed on day 4 of pregnancy. In both experiments, fetoplacental viability was ensured by treating the rabbits with medroxyprogesterone acetate (MPA). In both Exp 1 and 2, withdrawal of estrogen on day 21 of pregnancy caused a dramatic decline in serum progesterone concentrations by day 22. Serum progesterone concentrations remained low, and corpora lutea regressed, although viable fetuses were maintained with MPA. In animals not receiving MPA, estrogen withdrawal caused the loss of luteal function, followed by abortion on days 23-24. In contrast, estrogen replacement (via E2 implant) on day 22 in Exp 1 was fully capable of restoring serum progesterone concentrations to pretreatment values on days 24-27 in MPA-treated rabbits. In rabbits not receiving MPA, estrogen replacement also restored serum progesterone concentrations and prevented abortion. These results provide further evidence that estrogen is essential for normal luteal function in the pregnant rabbit. In the absence of estrogen, the rabbit placenta maintained by the progestagen MPA has no direct luteotropic activity.     

Different effects of the antiprogesterone RU486 on progesterone secretion by the corpus luteum of rats with 4- and 5-day oestrous cycles.

Administration of the antiprogesterone RU486 (2 mg/day) for 14 days to rats with a 5-day reproductive cycle resulted in an increase in both ovarian and pituitary weight in contrast with rats with a 4-day oestrous cycle. Luteal progesterone production decreased earlier in 4-day than in 5-day cyclic rats. Treatment of 5-day cyclic rats with antiprogesterone from the day of metoestrus onwards resulted in the advancement of the preovulatory prolactin surge by 24 h. Progesterone production by the corpus luteum was, however, not affected, indicating that in 5-day cyclic rats the corpora lutea are still functionally active at the time of the preovulatory surge of prolactin. They become, therefore, stimulated both in size and progesterone production. In contrast, the corpora lutea in 4-day cyclic rats are functionally inactive at the time of the preovulatory surge of prolactin, and prolactin acts luteolytically. In conclusion, the advancement of the preovulatory surge of prolactin by 24 h accounts, at least in part, for the increase in ovarian weight in 5-day cyclic rats after treatment with antiprogesterone. The results of these experiments do not agree with a direct effect of the antiprogesterone RU486 on progesterone secretion by the corpus luteum.