Reactivation of regressing corpora lutea by estradiol in the pregnant rat: dependence on placental lactogen.

Previous investigations have clearly demonstrated that estradiol maintains corpus luteum function. However, it is unknown whether estradiol can restimulate progesterone synthesis and/or growth of corpora lutea that have already undergone luteolysis. The present study was designed to determine 1) whether estradiol can reactivate the steroidogenic capacity and/or growth of corpora lutea that are deprived of luteotropic support, 2) whether estradiol affects progesterone metabolism, and 3) whether the action of estradiol is related to levels of rat placental lactogen in the peripheral circulation. Rats were hypophysectomized and hysterectomized on Day 12 of pregnancy and were treated between Days 12 and 15 with either estradiol (100 micrograms/day) or 1-cm testosterone implants. Both treatments are known to maintain luteal concentrations of estradiol at physiological levels. In vivo treatment with either estradiol or testosterone prevented the drop in progesterone production and maintained the concentration of serum progesterone at levels found in intact pregnant rats. This action was not due to an alteration in the rate of metabolism of progesterone to 20 alpha-hydroxyprogesterone, since peripheral serum levels and in vitro production of 20 alpha-hydroxyprogesterone were unaffected by estradiol. When testosterone treatment was started 24 and 48 h after hypophysectomy and hysterectomy, at a time when progesterone production had been markedly reduced and luteal growth had ceased, a restimulation of both progesterone synthesis and luteal growth was observed. However, in all cases the ability of estradiol to stimulate progesterone was finite, and corpora lutea ceased to respond by Day 17, coincident with the time that rat placental lactogen became undetectable in the circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential action of decidual luteotropin on luteal and follicular production of testosterone and estradiol.

Decidual tissue of the rat produces a hormone with physiological and biochemical characteristics similar to those of PRL. Because PRL affects both follicular and luteal production of testosterone and estradiol, it was of interest to determine whether decidual luteotropin affects basal and/or LH-stimulated ovarian secretion of steroids and whether it differentially affects follicular and luteal synthesis of testosterone and estradiol. The uteri of pseudopregnant adult rats were scratched on day 5 to induce decidual tissue formation. Pseudopregnant animals without decidua were used as controls. Rats were either hypophysectomized on day 8 or left intact. They were treated with 1.5 IU hCG/day or with vehicle between days 8-9. On day 9, blood was obtained from the ovarian vein, and both corpora lutea and large antral follicles were isolated and incubated in vitro. The presence of the decidua significantly suppressed both basal and hCG-stimulated ovarian secretion of estradiol, yet enhanced progesterone production. A similar inhibitory effect of decidual tissue on hCG stimulation of testosterone and estradiol was observed in the hypophysectomized rats. When the effect of decidua on follicles and corpora lutea was studied separately, it was found that follicles of rats with decidua produced significantly less testosterone and estradiol than follicles of rats without decidua. hCG administration to either intact or hypophysectomized rats markedly enhanced the follicular capacity to produce these two steroids. However, the degree of hCG stimulation of follicular steroidogenesis was significantly reduced by the presence of decidual tissue. In contrast, the decidua did not inhibit the in vitro steroidogenic capacity of corpora lutea. Luteal tissue of intact rats with or without decidua produced similar basal amounts of testosterone and estradiol and responded to a hCG challenge with comparable increases in the production of both steroids. After hypophysectomy, however, the responsiveness of corpora lutea to hCG stimulation differed in rats with or without decidual tissue. Whereas luteal cells of rats without decidual tissue gradually lost their responsiveness to hCG stimulation, luteal cells of rats with decidua remained highly responsive to hCG and produced high levels of testosterone and estradiol. In summary, the present investigation demonstrates that decidual luteotropin impairs ovarian secretion of estradiol and significantly inhibits the stimulatory effect of hCG on ovarian secretion of testosterone and estradiol.(ABSTRACT TRUNCATED AT 400 WORDS)

Identification and partial characterization of a prolactin-like hormone produced by rat decidual tissue.

Previous studies have strongly, but indirectly, suggested that rat decidual tissue produces a prolactin-like hormone, decidual luteotropin, which markedly affects luteal cell function. However, it was also found that extracts of decidual tissue do not cross-react with antisera to either rat or ovine prolactin (PRL). The purpose of this study was to determine whether the decidual tissue contains a substance that binds to PRL receptors in rat luteal membranes and, if so, to identify, quantitate, and characterize this molecule with the use of an ovarian radioreceptor assay. Decidual tissue was induced in day 5 pseudopregnant rats by scratching the antimesometrial wall of the uterus; it was collected on day 9 and homogenized and extracted. Decidual tissue extracts bound specifically to ovarian PRL receptors. Graded dilutions of the extracts yielded curves that were parallel to the ovine PRL standard, indicating that decidual luteotropin competes for the same receptor sites on rat luteal membranes. To determine the levels of decidual luteotropin throughout pseudopregnancy, decidual tissue was obtained on each day between days 6-12. The PRL-like activity was detectable in decidual tissue as early as day 6, reached a maximum on day 9, and declined thereafter. The elution profile obtained from gel filtration of a day 9 decidual tissue extract displayed a major component of decidual luteotropin eluting at a Ve/Vo ratio of approximately equal to 2.0. Column chromatography indicated that decidual luteotropin corresponds to a protein with a molecular weight of 23,500. The hormone was heat labile, digestible by trypsin, and appears to contain disulfide linkages. In summary, this study reports the identification, quantitation, and partial characterization of a PRL-like hormone produced by the decidual tissue of the rat.

Relationship between luteinizing hormone and decidual luteotropin in the maintenance of luteal steroidogenesis.

Between Days 6-11 of pregnancy or pseudopregnancy, the decidual tissue of the rat produces a prolactin-like hormone, decidual luteotropin, which can sustain luteal progesterone production when prolactin is suppressed. However, this effect is dependent upon the presence of the pituitary. The present investigation was undertaken to determine whether decidual luteotropin and luteinizing hormone (LH) act together to sustain luteal steroidogenesis and if so, to find out whether the need for LH is due to the inability of the decidual tissue to produce LH-like material and/or whether LH affects decidual luteotropin production. Pseudopregnant rats with or without decidual tissue were hypophysectomized on Day 8 and treated with either 1.5 IU human chorionic gonadotropin (hCG)/day or with vehicle. Within 24 h, serum progesterone dropped in both vehicle-treated groups and decidual luteotropin levels declined by 80% in the decidual tissue. Human CG administration had no effect on progesterone production in the control group. Yet in rats with decidual tissue, hCG stimulated progesterone production for at least 48 h and maintained the decidual tissue content of decidual luteotropin. Progesterone, but not hCG treatment, maintained decidual luteotropin concentrations in ovariectomized rats. To compare the luteotropic activity of the decidual tissue with that of the placenta, pregnant or pseudopregnant rats with decidual tissue were hypophysectomized on Day 8 and treated with 1.5 IU hCG. Control groups had decidual tissue or placentas removed and were similarly treated. Human CG stimulated progesterone production only in rats with placental or decidual tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential action and secretion of rat placental lactogens.

The abilities of the two different mol wt forms of rat placental lactogen (rPL) to maintain luteal steroidogenesis in pregnant rats in the absence of PRL were determined. The two forms of rPL present in day 12 pregnant rat serum were separated by gel chromatography, lyophilized, and reconstituted in a volume of saline equal to the original volume of serum. Rats were injected with 0.4 mg ergocryptine (ECO) on day 6 of pregnancy to suppress PRL and were then treated with a preparation of the large mol wt (LMW) hormone, the small mol wt (SMW) hormone, or both molecules (2 ml/day). Control animals received saline. Twice daily injections of the amount of LMW hormone contained in 1 ml day 12 pregnant rat serum reversed the abortifacient effect of ECO. In contrast, administration of the SMW hormone did not maintain either pregnancy or progesterone levels. Administration of both mol wt forms of rPL was also capable of maintaining luteal function. Sera obtained from day 18 pregnant rats containing only the SMW hormone had no luteotropic activity when administered, yet treatment with sera of day 12 pregnant rats sustained progesterone synthesis and fetal survival after ECO treatment. rPL were measured in the peripheral circulation and in the uterine vein throughout pregnancy by radioreceptor assay (RRA) using particulate membranes from either rabbit mammary gland or rat ovaries. Two peaks of activity were observed in the peripheral circulation by the two RRAs: one between days 11-14 and another between days 17-21, with a decline in activity between days 14-16. In contrast, levels of rPL in the uterine vein remained elevated throughout pregnancy. Concentrations of the LMW placental luteotropin were 5-10 times higher by ovarian RRA (O-RRA) than by mammary gland RRA (MG-RRA) between days 11-13, but concentrations of the SMW placental lactogen were found by the two RRAs to be similar in the later stages of pregnancy. Gel filtration of day 12 pregnant rat serum revealed two peaks of PRL-like activity. The O-RRA detected 19 times more LMW placental luteotropin than did the MG-RRA in the first peak of activity, yet measured equivalent amounts of the SMW placental lactogen in the second peak. Similar to results found in the peripheral circulation, levels of LMW placental luetotropin in the uterine vein measured by MG-RRA were significantly lower than those determined by O-RRA until day 14 of pregnancy.(ABSTRACT TRUNCATED AT 400 WORDS)