Maintenance Of Corpus Luteum Research Articles

Progesterone and LH variations after LH-RH administration in the luteal phase of the menstrual cycle.

We have investigated the pituitary and luteal responses to LH-RH and their related changes. 11 normal women were studied during the luteal phase (day +4/+11). Blood samples were collected every 15 min for a basal period of 180 and 120 min after the intravenous administration of 25 micrograms of LH-RH. Progesterone (P) and LH were assayed by radioimmunoassay. Data were analyzed as maximum peak and its percent increase (delta max), integrated secretory area (ISA) and percent increase of ISA (delta A) in respect to basal values for both P and LH. LH-RH elicited a secretory response of both hormones in all cases. ISA of LH was significantly greater after LH-RH administration in respect to basal values (p less than 0.001) and delta max accounted to 475 +/- (SE) 36% of the basal concentration. Luteal responsiveness varied from about 115-130% to more marked increments. ISA of P differed from basal to stimulated conditions (p less than 0.05) and delta max was 166 +/- (SE) 14%. The analysis of temporal relationship between P and LH secretion showed that LH promptly rose after LH-RH, while the enhancement of P plasma levels occurred within 31 +/- 19 min after LH rise. Then P levels reached a plateau, values of which were statistically different from those observed before LH-RH administration. In two cases where luteal function was blunted or absent, in spite of marked increments of LH, P secretion did not occur. These data are consistent with the presence of close relationships between hypothalamic, pituitary and luteal functions and strengthen the contention about the usefulness of LH-RH during luteal phase for the lifespan and maintenance of corpus luteum.

Control of corpus luteum function in the pregnant rabbit: role of the placenta ("placental luteotropin") in regulating responsiveness of corpora lutea to estrogen.

Experiments were performed to examine the interaction between estrogen and "placental luteotropin," the two luteotropins thought to be required for corpus luteum maintenance in the pregnant rabbit. Experiment 1 was designed to determine whether estrogen alone was luteotropic in the absence of "placental luteotropin." Pregnant rabbits were assigned to the following groups: Group A, sham hysterectomy; Group B, hysterectomy; Group C, hysterectomy plus estradiol on Day 20; and Group D, hysterectomy plus estradiol on Day 22. "Placental luteotropin" was removed on Day 21 of pregnancy by hysterectomy and estrogen was administered via an estradiol-filled Silastic implant which was placed s.c. before (Day 20, Group C) or after (Day 22, Group D) hysterectomy. Daily blood samples were taken for radioimmunoassay of serum progesterone and estradiol concentrations. Corpus luteum weights were measured at autopsy on Day 27. Hysterectomy caused serum progesterone concentrations to fall rapidly from 13 +/- 1 ng/ml on Day 21 to 2 +/- 1 ng/ml on Day 23, and to 1 ng/ml or less on Days 24-27. In sham hysterectomized rabbits (Group A), pregnancy was maintained and serum progesterone concentrations remained elevated at 9-15 ng/ml throughout (Days 20-27). Estradiol treatment (Groups C and D) did not prevent or reverse luteal regression induced by hysterectomy and serum progesterone concentrations declined in a similar fashion to Group B. Serum estradiol concentrations were 4-8 pg/ml in all groups and did not vary substantially with stage of pregnancy or treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Biochemical aspects of conceptus--endometrial interactions.

Mammalian conceptuses must provide a chemical signal to the maternal system to insure maintenance of corpus luteum (CL) function and of progesterone production and continuation of uterine endometrial secretory activity. These events insure that the developing conceptus is provided with appropriate nutrients, regulatory enzymes and endocrine state to allow successful establishment and maintenance of pregnancy. Pig blastocysts begin to produce estrogens by Day 11 of pregnancy, which prevents secretion of the uterine luteolytic factor (PGF2 alpha) in an endocrine direction, but allows secretion in an exocrine direction, i.e., into the uterine lumen. Therefore, CL are "protected." Blastocyst estrogens also trigger secretion of a group of proteins, including uteroferrin, an iron transport protein, and a family of protease inhibitors whose biosynthesis within the uterine glandular epithelium is under the control of progesterone. Estrogen also appears to promote accumulation of glucose and fructose within the uterine lumen. A complex in vivo "culture medium" is thereby established to promote conceptus development. Pig blastocysts do not undergo invasive implantation within the uterine lumen although they produce the protease, plasminogen activator. Invasion may be prevented by endometrial secretion of progesterone-induced protease inhibitors which are produced in large amounts. In addition to estrogens of conceptus origin, calcium and prostaglandins PGF2 alpha and E2 may affect the uterine vasculature, water and electrolyte transport, capillary permeability, conceptus steroid production, and related events during pregnancy. The blastocysts of the large domestic animals also secrete proteins which include a large glycoprotein (Mr approximately 600,000) and a small acidic protein (Mr approximately 17,000). The latter has been purified from sheep and named ovine trophoblast protein I. These proteins may play unique roles in early pregnancy with respect to establishment and maintenance of pregnancy in the ewe, sow, mare, and cow.

Luteal luteinizing hormone receptors during the postovulatory period in the mare.

Changes in serum luteinizing hormone (LH) and progesterone concentrations, number of luteal unoccupied LH receptors, receptor affinity constants, luteal weights and luteal progesterone concentrations were determined during the postovulatory period in the mare. The number of unoccupied LH receptors and receptor affinity was less during the early (Days 1-4) and late [Day 15 through 3rd day after start of corpus luteum (CL) regression] luteal phases than during the mid-luteal (Days 9-14) phase of the postovulatory period (P less than 0.01). The number of LH receptors per CL increased 21-fold (P less than 0.001) from Day 1 to Day 14. Receptor affinity increased 5-fold (P less than 0.001) from Day 1 to Day 13. Receptor number was highly correlated with receptor affinity (P less than 0.01) and both were highly correlated with serum and luteal progesterone (P less than 0.01). During regression of the CL, the number of LH receptors and receptor affinity decreased concomitantly with serum and luteal progesterone. Morphologically, luteal cell development and degeneration correlated with the change in receptor numbers, affinity constants and luteal and serum progesterone concentrations. Receptor number and affinity, luteal weight and serum and luteal progesterone concentrations did not differ between the CL from multiple ovulations. Random variations in the data observed between CL from multiple and single ovulations suggested that CL from the two groups were not different in structure and function. In summary, the above results suggest that major factors in regulation of progesterone secretion and maintenance of the equine CL are changes in the number of LH receptors and the affinity constants throughout the postovulatory period.

Aspects concerning the role of prostaglandins for ovarian function.

The present review briefly summarizes the current view of the mechanisms whereby prostaglandins (PGs) may act to modulate ovarian function. Particular concern is devoted to the aspects of ovarian function which are under current investigation by the authors, namely follicular maturation and rupture, granulosa cell and oocyte maturation, and the formation and maintenance as well as the regression of the corpus luteum (CL). PGs are formed in the granulosa cells of the preovulatory follicle in response to gonadotropin action and are at their highest levels around the time of ovulation. PGs are believed to be obligatory for follicular rupture, but their mechanism of action is still unknown. In the process of oocyte maturation PGs can mimic the stimulatory effects induced by LH or hCG, but are probably not obligate mediators of these effects. The importance of PGs for CL formation and maintenance is so far unsettled, and PGs may be regarded more as modulators than as inducers for these processes. The most well-documented effect of PGs is the induction of CL regression. Evidence is presented that PGs may have this effect also in the human.

Corpus luteum function after indomethacin treatment during the estrous cycle and following hysterectomy in the gilt.

Indomethacin (IND), a prostaglandin synthetase inhibitor, was used to determine the relationship between prostaglandin (PG) secretion and corpus luteum (CL) function during the luteal phase of the estrous cycle and after hysterectomy in the gilt. In Experiment 1, gilts that had displayed estrous cycles of 18 to 22 days (onset of estrus = Day 0) were randomly assigned to four treatments (n = 7/group): 1) ethanol vehicle (EtOH) daily from Day 10 through Day 17; 2) IND daily from Day 10 through Day 17;3) IND daily from Day 10 through Day 13 and EtOH daily from Day 14 through Day 17; and 4) EtOH daily from Day 10 through Day 13 and IND daily from Day 14 through Day 17. In Experiment 2, 15 gifts were hysterectomized on Days 6 to l0 of the estrous cycle and were randomly assigned to a control (n = 7) or IND-treated (n = 8) group. Treatment, daily for 4 days, began when all gilts had reached Day 18 or later. The daily dose of 10 mg IND/kg BW was calculated on the average body weight of each treatment group. In Experiment 1, ovarian morphology at necropsy on Day 25, serum progesterone and 13,14-dihydro-15-keto prostaglandin F2α (PGFM) concentrations throughout the experimental period, and failure to display estrus by Day 25 suggest that IND treatment during the luteal phase of the estrous cycle prolonged CL maintenance in the pig. The progesterone and PGFM assays were validated in our laboratory. In experiment 2, CL morphology and serum progesterone and luteinizing hormone (LH) concentrations indicate that IND treatment failed to affect luteal function by a direct action on the luteal cell or by suppressing pituitary LH secretion.

Unilateral uteroovarian relationship in pregnant cattle and role of uterine vein

The hypothesis of a unilateral uteroovarian relationship between location of embryos and maintenance of corpora lutea (CL) was tested in superovulated cattle. Ovulations were induced in both ovaries and a uterine horn was isolated subsequent to insemination to produce unilateral pregnancy. The mean weight of CL on day 24 was greater (P<.05) on the gravid side (2580 mg) than on the nongravid side (1200 mg; n=5), supporting the hypothesis. Involvement of the main uterine vein in the unilateral pathway between a gravid horn and the adjacent ovary was demonstrated in an experiment which utilized separation of uterine horns, anastomosis of uterine veins between sides, and insertion of embryos into one side by embryo transfer. Mean weight of CL on day 24 was less (P<.05) when the gravid horn was contralateral to the CL (950 mg; n=3), than when the gravid horn was ipsilateral to the CL (4760 mg) or when the gravid horn was contralateral to the CL and the uterine vein from the contralateral side was anastomosed to the vein on the ipsilateral side (3580 mg; n=3).

Corpus luteum maintenance during early pregnancy in the cow.

Holstein heifers (18 pregnant, 12 inseminated but non-pregnant, and 17 cyclic) were studied during the first 18 days after oestrus. Jugular vein plasma progesterone concentrations were significantly (P < 0.05) higher in pregnant than in non-pregnant and cyclic animals between Days 10 and 18. Jugular oestradiol concentrations were also higher in pregnant than in cyclic animals between Days 6 and 16 (P < 0.05). No differences were found among the three groups in jugular LH levels during Days 1-18. Ovarian and uterine vein progesterone and oestradiol concentrations suggested that the elevated peripheral plasma concentrations of these steroids in pregnant animals were due mainly to increased ovarian production, but the embryo itself may have contributed to the oestradiol levels found at Day 17. Luteal tissues from pregnant animals contained more progesterone when incubated alone or with LH than tissues from cyclic animals (P < 0.06). However, LH-stimulated synthesis (incubated with LH minus incubated alone) was nearly identical for the three groups of tissues. Therefore, loss of responsiveness to LH does not appear to be the initial event in luteolysis. Concentrations of PGF in ovarian arterial plasma in cyclic and pregnant animals were similar at Day 18, although uterine vein concentrations were higher (P < 0.05) in the cyclic animals. Free arachidonic acid concentrations in corpora lutea at Day 18 were higher (P < 0.05) in cyclic than in pregnant animals. The data suggest that the embryo may produce one or more luteotrophic substances that stimulate increased progesterone secretion by the corpus luteum beginning as early as Day 10 of pregnancy.

Maintenance of the Corpus Luteum of Early Pregnancy in the Ewe. I. Luteotropic Properties of Embryonic Homogenates

Experiments were carried out to examine the Iuteotropic properties of embryonic homogenates in ewes. Homogenates prepared from embryos collected 14-15 days postcoitum were infused into the uterine lumen of cycling ewes (n = 4) from Days 12 through 18 postestrus. Four control ewes received isotonic saline only. Embryonic homogenate, infused at a rate of 3 embryonic equivalents/24 h, prolonged the lifespan of corpora lutea through Day 18 postestrus. Mean serum progesterone levels on Days 16, 17 and 18 were 2.2 ± 0.5 ng/ml (±SEM), 2.0 ± 0.4 ng/ml and 1.6 ± 0.4 ng/ml in the treatment group and 0.33 ± 0.29 ng/ml 0.04 ± 0.01 ng/ml and 0.06 ± 0.01 ng/mI in the control group. Luteal weights on Day 18 were 626 ± 22 mg in the treatment group and 194 ± 46 mg in the control group. To determine if the luteotropic property of embryonic homogenate was due to the presence of Ll-I or prolactin-like molecules, we examined embryonic protein in sensitive radioreceptor assays for these hormones. However, 100 pg of embryonic protein had no activity in either the LH-hCG or prolactin radioreceptor assay. In a second study, 100 pg of embryonic protein had no effect on synthesis of progesterone or cAMP in dispersed ovine luteal cells, either alone or in combination with LH and/or prolactin. Synthesis of both progesterone and cAMP could be stimulated in these cells by NIH-LH-S19. The data indicate that homogenates of 14-15-day-old embryos are capable of prolonging luteal function when infused into the uterine lumen, but the effect does not appear to be exerted via an LH or prolactin-like molecule.

Uteroovarian Pathways and Maintenance of Early Pregnancy in Rhesus Monkeys1

To evaluate the possibility that corpus luteum (CL) maintenance may be regulated by the local transfer of materials from the uterus to the ovary near the time of implantation in primates, rhesus monkeys were laparotomized on Days 17-18 of pregnancy and all anatomical connections between the ovary bearing the CL and the uterus were severed. This technique was designed to prevent local uteroovarian transfer while maintaining ovarian blood flow via the ovarian artery and vein. Sham ligated animals (n = 2) maintained pregnancy; however, based on serum concentrations of progesterone and macaque chorionic gonadotropin (mCG), 4 of 6 experimental females aborted within 48 h following surgery. Abortion in the experimental animals suggested that either 1) a local uteroovarian pathway was involved in the maintenance of early pregnancy or 2) that the loss of the blood supply to the ovary from the uterine artery had a detrimental effect on CL function. To determine which of these conclusions was correct, a second experiment was conducted. Monkeys were laparotomized on Days 13-14 of pregnancy and the uterine vein was ligated at the utero-vaginal and utero-tubal junction of the uterus on the side ipsilateral (n = 4, experimental) or contralateral (n = 2, control) to the ovary bearing the CL. Sham ligation on the ipsilateral side (n = 2) was also performed. Experimental treatment was expected to block a local uteroovarian pathway while not compromising ovarian arterial blood flow. All animals maintained pregnancy. We conclude, therefore, that a local uteroovarian pathway is not required for maintenance of early pregnancy in the rhesus monkey.

Prostaglandin F2 alpha and progesterone synthesis in vitro by bovine corpora lutea of early pregnancy.

The rapid regression of the bovine corpus luteum at the 17th–19th day of the estrous cycle requires the presence of the uterus and appears to be mediated by estrogen and one or more uterine luteolysins acting locally on the ipsilateral corpus luteum (1,2). Little information is available as to how the presence of a viable embryo in the uterus causes maintenance of the bovine corpus luteum. Del Campo et al. (3) suggested a local relationship between a gravid uterine horn and the adjacent ovary in the pregnant cow. Although the corpus luteum is necessary for maintenance of pregnancy in the cow, at least until Day 236 (4), the transition of the cyclic corpus luteum to the corpus luteum of pregnancy occurs before the embryo implants. Staples et al. (5) showed that very rapid elongation of the trophoblast occurs at about Day 15, just prior to the time of cyclic corpus luteum involution. Mesoderm formation also begins at Day 15, and the bi-nucleated giant cells of the trophoblast (6) first appear at this time (5). Greenstein et al. (7) suggested that these cells may play a role in stimulating maintenance of the corpus luteum of pregnancy. These facts suggest that the developing embryo either inactivates the normal uterine luteolytic mechanism, or produces a potent luteotrophin that overcomes this mechanism.

Gonadotropin in follicular phase in women with luteal phase defect.

Serum FSH and LH in women with luteal phase defect were measured. Their serum FSH and LH were lower than those in normal women and higher than those in women with amenorrhea. Administration of clomiphene citrate to the women with luteal phase defect were effective in 2/3 of the cases. These results are consistent with the hypothesis that a relative deficiency of FSH during the follicular phase results in diminished follicular development and subsequent inadequate corpus luteum maintenance.

The effect of human chorionic gonadotropin and estradiol-17β on the maintenance of the human corpus luteum of early pregnancy

The effect of exogenous human chorionic gonadotropin (HCG) and estradiol valerate (EV) on the maintenance of the corpus luteum of early pregnancy, assessed by serial estimations of serum progesterone and 17α-hydroxyprogesterone (17-OHP), was studied in 35 subjects following therapeutic termination of pregnancy by suction curettage before the tenth week of gestation. Continuous intravenous infusion of 50,000 International Units (I.U.) of HCG for 24 hours following termination of pregnancy delayed the decline of serum HCG levels, and 17-OHP levels were maintained at preoperative levels for the 24 hours of the infusion. Single intramuscular injections of 5,000 or 20,000 I.U. of HCG were ineffective. Administration of 25 mg. of EV intramuscularly immediately following therapeutic termination of pregnancy slightly retarded the decline of serum 17-OHP levels. The same treatment when administered in combination with the intravenous infusion of 50,000 I.U. of HCG completely prevented the ability of HCG to maintain serum levels of 17-OHP. These findings suggest an antagonism between estradiol and HCG in maintenance of the human corpus luteum during early pregnancy.

Mechanism of action of luteinizing hormone and follicle-stimulating hormone on the ovary in vitro

The mechanism of action of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) upon various cell types of the mammalian ovary is reviewed. Emphasis is placed upon in vitro studies using organ and cell culture as well as short-term incubations. FSH and LH actions upon the following ovarian functions are discussed: steroidogenesis and metabolism of the ovary as a whole and of the isolated follicle and its component cell types, the granulosa and thecal cells, as well as folliculogenesis and follicular growth, oocyte maturation, follicular rupture, and corpus luteum maintenance and steroidogenesis. The roles of gonadotropin receptors, AMP, prostaglandins, protein kinase, and protein synthesis in these LH and FSH actions are discussed. Intraovarian regulation of LH and FSH action is reviewed, including a discussion of the possible roles of follicular fluid inhibitors upon oocyte maturation and granulosa cell luteinization.

Vaginal stimulation and progesterone: relation to corpora lutea maintenance, pregnancy and parturition in the hamster.

Hamster ovaries were examined under various natural and experimental conditions involving progesterone administration and its possible influence on parturition was oncsidered. Pregnancy was artificially induced in some without vaginal stimulation and 5 or 10 mg of progesterone were given. In others vaginal stimulation was done and the same doses of progesterone given at the time of artificially induced pregnancy. OVaries were removed on Day 5 9 or 13 and following parturition on Day 16. If parturition did not occur on Day 16 ovaries were removed on Day 17. Oxytocin given on Day 17 to females overdue in delivery had no effect. In females made pregnant without vaginal stimulation but with progesterone given all corpora lutea had regressed by Day 9 and ovarian weight had diminished. Those having received 10 mg of progesterone showed earlier changes in ovaries and corpora lutea. All these females remained pregnant until term but then an inhibition of parturition was noted. Mature Graafian follicles were present in all ovaries. In those whose vaginae had been stimulated artificially and progesterone given at the time of induced pregnancy the corpora lutea did not regress nor were the ovaries affected. In these females parturition proceeded normally. It is thought that progesterone inhibits gonadotropin release necessary for the functional maintenance of the ovary and corpora lutea. Some of the progesterone however persists to adequately maintain pregnancy. A factor necessary for parturition is also inhibited by progesterone. Adequate stimulation of the vagina prevents these adverse effects. Vaginal stimulation is thought to activate the luteotropic complex. In the hamster normal gestation and parturition seem to require a continued supply of luteotropic hormones and possibly ovarian factors for parturition.

Studies on Luteolysis: Effect of Antiserum to Luteinizing Hormone on Sterols and Steroid Levels in Pregnant Hamsters

The effect of luteinizing hormone antiserum (LH A/S) on sterol and steroid levels in luteal and non-luteal ovarian compartments, and on serum steroid levels of pregnant hamsters, was studied. Injection (ip) of 0.1 ml of LH A/S on day 7 caused termination of pregnancy and morphological regression of the corpus luteum (CL) within 18-20 h of treatment, whereas LH-free non-immune serum had no effect. Within 3 h of administration of LH A/S the luteal progesterone levels fell from a control value of 36.0 +/- 2.4 to 15.6 +/- 3.4 ng/mg, and estrogen from a control value of 20.8 +/- 3.4 to 12.2 +/- 1.5 pg/mg. By 12 h progesterone had dropped to 7.3 +/- 0.3 ng/mg whereas estrogen was undetectable by radioimmunoassay. Serum progesterone fell in 3 h from 5.53 +/- 0.39 to 3.15 +/- 0.26 ng/ml whereas estrogen fell from 172 +/- 26 to 123 +/- 9 pg/ml. The progesterone content of non-luteal ovarian tissue dropped in 3 h from 1.06 +/- 0.01 to 0.47 +/- 0.06 ng/mg and estrogen from 115.0 +/- 1.5 to 11.0 +/- 0.65 pg/mg. Both progesterone and estrogen were undetectable at 24 h. In the CL, free cholesterol concentration did not change significantly after A/S treatment, while esterified cholesterol increased from 2.82 +/- 0.14 to 4.14 +/- 0.25 mug/mg within 6 h and 5.52 +/- 0.17 mug/mg by 12 h. The results suggest that LH plays a critical role in the maintenance of CL of early pregnancy in the hamster and that deprivation of LH, even for periods as short as 3 h, significantly influences steroid production. The accumulation of cholesterol esters following LH-deprivation suggests that loss of cholesteryl esterase activity could be one of the events leading to luteolysis.

Corpus luteum maintenance in gilts during hypothalamic suppression with AIMAX.

Two trials were conducted using crossbred gilts randomly assigned to three treatments: AIMAX+sham hysterectomy (AS); AIMAX+hysterectomy (AH) and hysterectomy (H). Gilts were hysterectomized or sham hysterectomized on day 8 to 10. In trial I, AS (15) and AH (20) gilts were fed 125 mg AIMAX per day from day 2 to 31. Group H (15) were fed the control diet without AIMAX. All gilts were necropsied on day 32. In trial II, AH gilts (10) were fed 125 mg AIMAX per day from day 20 to 39 and H gilts (7) were fed the control diet without AIMAX. All gilts were necropsied on day 40. In trial I, corpora lutea (CL) regressed in all AS gilts, but CL were maintained in all H gilts. However, only 9 of 20 AH gilts maintained corpora lutea. The degree of CL maintenance was reflected in the total ovarian weights in each treatment. Average weight of maintained CL of AH gilts was significantly (P<.01) lower than that of H gilts. In trial II, CL were maintained in all gilts. The ovarian weights of the AH gilts were nonsignificantly lower than the H gilts. Average CL weight of the AH gilts was significantly (P<.05) lower than that of H gilts. The cellular morphology of all maintained CL in both trials was similar. It was suggested that changes in the luteal tissue which allow CL maintenance beyond the luteal phase of the estrous cycle occur at day 16 to 20 and that AIMAX treatment from day 2 to 31 probably suppressed these “critical” changes. Therefore small CL were maintained in only 9 of 20 gilts. By starting AIMAX on day 20, these changes in the CL were not inhibited. Therefore CL were maintained in 10 of 10 gilts. Luteinizing hormone secretion was probably suppressed but not completely blocked by AIMAX. Therefore, minimal amount of LH were probably available to act alone or in combination with prolactin to produce the luteal maintenance observed in this study.

The effect of antisera to bovine LH in hysterectomized and intact heifers.

Injection of antiserum to bovine LH into hysterectomized heifers caused significant decreases in corpus luteum weight, total progesterone, total progestins and 20�-hydroxypregn4-en-3-one (204-01) concentration but had no effect on progesterone concentration. Gonadotropin secreting cells in the anterior pituitaries of these heifers were markedly degranulated and pituitary LH contents lowered. Thyroid epithelial cell heights were lowered suggesting that the antiserum also contained anti-TSH. The administration of antibovine LH to cyclic heifers from Day 2 to Day 6 of the cycle caused a significant decrease in corpus luteum weight and total progesterone content, but only a slight decrease in progesterone concentration. Histological signs of regression were clearly evident in the corpora lutea of the hysterectomized anti-LH treated heifers, but little difference could be noted between the corpora lutea of control and treated cyclic animals. Injection of 50 ml of antibovine LH daily from Day 2 to Day 6 of the cycle increased the interval between corpus luteum removal at Day 11 and return to estrus. Injections of 50 ml of antibovine LH daily from Day 12 to Day 16 and from Day 16 to Day 20 of the cycle increased the lengths of the treatment cycles to 28.5 and 36.7 days, respectively. The first post-treatment cycle in both groups was significantly shortened. The increase in cycle length was primarily due to a failure of follicles to develop to mature size, rather than to prolongation of the life span of the corpora lutea. The results of these experiments indicated that LH is required for follicular development and maturation and for the induction of estrus, as well as for corpus luteum maintenance.

Maintenance of corpora lutea and pregnancy in hypophysectomized rabbits.

Hypophysectomy during the second week of gestation resulted in severe follicular involution and degeneration of the corpora lutea (CL). Within 7 days, no progesterone could be detected in the ovarian effluent, and implant sites were the only remaining evidence of pregnancy. Degeneration of the interstitial tissue (1ST) was less evident; although little or no basal 20α-hydroxypregn-4-en-3-one (20α-OH) secretion was measurable, substantial amounts of this steroid (but no progesterone) were secreted following acute LH stimulation. None of the pituitary gonadotrophins (LH, FSH, or prolactin) supported luteal function when administered individually, but each one exerted a specific effect on ovarian structure and function: LH, in doses of 150 or 250 μg/X2 daily sc, depleted 1ST cholesterol and induced ovarian atrophy; FSH, 200-500 μ/X2 daily sc, stimulated follicular growth; and prolactin, 500μg/X2 daily sc, produced 1ST hypertrophy. When prolactin was combined with FSH (either with or without 5-20μg/ of LH), p...

Effect of hypophysectomy on the formation and maintenance of corpora lutea in the ewe.

Complete hypophysectomy on the day of ovulation in the ewe invariably prevented the formation of corpora lutea, and luteal regression occurred by day 12 in ewes completely hypophysectomized on day 5. Luteal function was also destroyed in approximately half of the incompletely hypophysectomized animals. Normal cyclic animals with spontaneous ovulations and anestrous animals in which ovulations were induced responded to hypophysectomy in a similar manner. It was concluded that pituitary support is necessary throughout the estrous cycle for normal formation and maintenance of corpora lutea in the ewe. (Endocrinology 82: 753, 1968)