Luteolysis In Rats Research Articles

The involvement of NR4A1 and NR4A2 in the regulation of the luteal function in rats

The nuclear receptor 4A (NR4A) members play important roles in cellular proliferation, differentiation and apoptosis. The current study first evaluate the expression of ovarian NR4A1 during different luteal stages in rats. Immature rats aged 28 days were treated with sequential Pregnant mare serum gonadotropin (PMSG) (D -2) / human chorionic gonadotropin (hCG) (D 0) to induce pseudopregnancy. Serum progesterone (P4) and ovarian expression of NR4A1 were detected by RIA and WB, respectively, at follicle stage (D 0), early (D 2), middle (D 7) and late (D 14 and D 20) luteal stages. To confirm the role of NR4A1 during the luteal regression, rats were treated with prostaglandin F2α analog (PGF) for 0–8 h on D 7 to detect the expressions of NR4A1 and NR4A2. RIA result showed that serum P4 reached highest level on D 7 and then declined. WB results showed that there were two types of NR4A1 (NR4A1-L and NR4A1-S) expressed in the ovary. The ovarian NR4A1-L decreased at the late luteal stage (D 20). However, the NR4A1-S increased at the late luteal stage (D 14). After PGF treatment on D 7, the expression of NR4A1-S increased which peaked at 0.5–1 h and then declined; while NR4A1-L expression did not change within 8 h. Real-time PCR results showed that the ovarian NR4A1 mRNA increased within 0.5 h, maintained high at 1 h and then declined. The NR4A2 mRNA expression exhibited a similar pattern to that of NR4A1 mRNA, though its abundance was not as high as NR4A1. IHC results revealed that NR4A1-L was expressed mainly in the cytoplasm of luteal steroidogenic cells, faintly expressed in the follicle theca cells, oocytes and the pericytes; while NR4A2 was primarily localized in the cytoplasm of luteal steroidogenic cells. In conclusion, all these results demonstrate that NR4A2 as well as NR4A1 might be involved in the luteal development and luteolysis in rats.

Differential Morphological Effects in Rat Corpora Lutea among Ethylene Glycol Monomethyl Ether, Atrazine, and Bromocriptine

Ethylene glycol monomethyl ether (EGME) or atrazine induces luteal cell hypertrophy in rats. Our previous study suggested that EGME stimulates both new and old corpora lutea (CL), while atrazine stimulates new CL. Bromocriptine (BRC) is known to suppress the luteolysis in rats. This study investigated the light- and electron-microscopic luteal changes induced by EGME, atrazine, or BRC. Female rats were treated with EGME (300 mg/kg/day), BRC (2 mg/kg/day), EGME and BRC (EGME + BRC), or atrazine (300 mg/kg/day) for 7 days. Luteal cell hypertrophy induced by EGME, EGME + BRC, and atrazine was subclassified into the following two types: CL hypertrophy, vacuolated type (CL-V) characterized by intracytoplasmic fine vacuoles, and CL hypertrophy, eosinophilic type (CL-E) characterized by eosinophilic and abundant cytoplasm. The proportions of CL-V and CL-E were different among the treatments. BRC-treated old CL showed lower proportion of endothelial cells and fibroblasts than normal old CL. Ultrastructural observation revealed that the luteal cells of CL-V contained abundant lipid droplets, whereas those of CL-E in EGME and EGME + BRC groups showed uniformly well-developed smooth endoplasmic reticulum. No clear ultrastructural difference was observed between the control CL and atrazine-treated CL-E. These results indicate that EGME, atrazine, and BRC have differential luteal morphological effects.

Estrogenはラット性周期黄体のMetastinと性腺刺激ホルモン放出ホルモン(GnRH)の発現を促進して黄体退行を引き起こす

Estrogenはラット性周期黄体のMetastinと性腺刺激ホルモン放出ホルモン(GnRH)の発現を促進して黄体退行を引き起こす

Reactive oxygen species mediate leukocyte-endothelium interactions in prostaglandin F2alpha -induced luteolysis in rats.

We investigated the contribution of neutrophils to prostaglandin (PG)F(2 alpha)-induced luteolysis and the role of reactive oxygen species (ROS) as potential mediators of neutrophil accumulation in regressing corpora lutea of superovulated rats. On day 8 of pseudopregnancy, subcutaneous injection of PGF(2 alpha) (500 microg) significantly increased rhodamine 6G-labeled leukocyte adhesion in luteal venules, as observed by intravital microscopy. Neutrophil accumulation was confirmed by significantly increased myeloperoxidase (MPO) activity. Pretreatment with anti-leukocyte antibody (CD18-directed monoclonal antibody, WT-3) significantly inhibited the PGF(2 alpha)-induced increases in adherent leukocytes and MPO activity. Anti-leukocyte antibody also maintained serum progesterone concentrations. Pretreatment with oxygen free radical scavengers, superoxide dismutase (50,000 U/kg) and catalase (90,000 U/kg), also attenuated these PGF(2 alpha)-induced alterations. Corpora lutea preloaded with dichlorodihydrofluorescein diacetate succinimidyl ester, a fluorescent indicator for determining intracellular ROS generation, exhibited an increase in fluorescence after PGF(2 alpha) treatment. These findings suggest that leukocyte-endothelium interactions mediated by ROS generation are important in PGF(2 alpha)-induced luteolysis in rats.

Dexamethasone and Indomethacin Inhibition of Structural Luteolysis in Rats: An Intraluteal Mechanism Involving Prolonged Activation of Phospholipase A2 Activity and Prostaglandin Synthesis May Facilitate the Luteolytic Process.

We previously showed that luteal cytosolic phospholipase A2 and prostaglandin F2α level which rises during functional luteolysis persisted during the following structural luteolysis in rats. To investigate the possible role of the sustained activation of luteal prostaglandin synthesis in the accomplishment of luteolysis, we studied the influence of systematic injection with a phospholipase A2 inhibitor, dexamethasone, and a cyclooxygenase inhibitor, indomethacin, on structural luteolysis. Repeated administration of the inhibitors to mothers for seven days postpartum partially reversed suckling stimuli-induced decline in pregnant corpus luteum weight. The inhibitors also inhibited exogenous prolactin-induced structural regression in immature pseudopregnant rats, and the inhibition of luteal cytosolic phospholipase A2 activity and prostaglandin F2α level was confirmed in this experimental model. Immunohistochemical study revealed that dexamethasone-treated corpus luteum had a significantly lower number of infiltrating macrophages. Moreover, fibroblastic proliferation in that corpus luteum seemed to be attenuated by both dexamethasone and indomethacin. Considered together with our previous findings, the data suggest that the persistent activation of luteal phospholipase A2 activity and prostaglandin generation may function to facilitate the luteolytic process and that this mechanism mediates prolactin-induced structural luteolysis in rats.

Gonadotropin-releasing hormone agonist has the ability to induce increased matrix metalloproteinase (MMP)-2 and membrane type 1-MMP expression in corpora lutea, and structural luteolysis in rats.

Gonadotropin-releasing hormone (GnRH) and its agonist analog (GnRHa) are well known to have luteolytic effects. We previously reported that prolactin (PRL) stimulated matrix metalloproteinase (MMP)-2 activity to degrade collagen type IV as a mechanism of structural luteolysis. The effects of GnRHa treatment on developed corpora lutea are unknown. In this study we assessed the effect of GnRH on MMP expression and induction of structural involution of developed corpora lutea of superovulated rats using GnRHa. Pregnant mare serum gonadotropin-human chorionic gonadotropin (hCG)-synchronized ovulation and luteinization were induced in immature female rats, followed by daily treatment with GnRHa from 5 days after hCG treatment. GnRHa-induced involution of corpora lutea was evident 3 days after the treatment, as shown by their markedly smaller size (60% of the control weight). Nine days after hCG injection, serum progesterone and 20alpha-dihydroprogesterone concentrations were as low as those associated with structural luteolysis. These findings revealed that GnRHa has the ability to induce structural luteolysis in superovulated rats in the same way that PRL does. To gain information on mechanisms of luteal involution induced by GnRHa, we performed gelatin zymography. This showed a significant increase in the active form of MMP-2 in the luteal extract of GnRHa-treated rats (more than twofold that of the control). Activation of pro-MMP-2 by membrane type-MMP (MT-MMP) is reported to be a rate-limiting step for catalytic function. Another function of MT-MMP is to degrade collagen types I and III. The plasma membrane fraction of corpora lutea of GnRHa-treated rats activated pro-MMP-2 of fetal calf serum, resulting in a marked shift of the 68-kDa band to the 62-kDa band in the zymogram. A Northern hybridization study also revealed simultaneous significant increases in expression of MMP-2 mRNA and MT1-MMP mRNA in corpora lutea of GnRHa-treated rats (more than threefold the control level). In summary, hormonal and histological features of corpora lutea of GnRHa-treated superovulated rats correspond to those of structural luteolysis. GnRHa stimulated the expression of MMP-2 and MT1-MMP in developed corpora lutea associated with involution. These findings support the conclusion that MMP-2, activated by MT1-MMP, and MT1-MMP itself, remodel the extracellular matrix during structural luteolysis induced by GnRHa.

Fas/Fas Ligand System in Prolactin-Induced Apoptosis in Rat Corpus Luteum: Possible Role of Luteal Immune Cells

The prolactin (PRL) surge in cycling rats during the proestrous afternoon is an inducer of apoptotic cell death in luteal cells. This luteolytic action of PRL is peculiar, because PRL may be categorized as a survival factor, if other known physiological functions of PRL are taken into account. Here we analyzed the underlying molecular/cellular mechanisms of this PRL-induced apoptosis. Corpora lutea (CL) were prepared from the ovary on the proestrous day and cultured with or without PRL (2 μg/ml). An addition of PRL to the culture medium induced DNA breakdown in the nuclei of cells mostly identified as steroidogenic by 3β-HSD activity staining, and the number of 3β-HSD-positive cells were significantly decreased, indicating the induction of apoptotic cell death by PRL among luteal cells in culture. Next, the expression of membrane form-Fas ligand (mFasL) in the luteal cell lysate was quantified, because Fas receptor is known to have an exact physiological role in luteolysis. An addition of PRL increased the expression of mFasL. Immunostaining and TUNEL assay on regressing CL revealed that both CD3-positive cells and FasL-positive cells were co-localized in the regions where apoptosis convergently occurred. Moreover, an addition of concanavalin A (ConA), a T-cell specific activator, to the culture mimicked the PRL action by inducing apoptosis in luteal cells and enhancing the expression of mFasL. These data suggest that the CD3-positive T lymphocyte in the CL is at least one of the PRL-effector cell species during the process of luteolysis in rats, and that FasL expression of these cells is upregulated by PRL.

The Effects of Growth Hormone on Corpus Luteum of Superovulated Rats

In general, growth hormone acts as a factor promoting cell proliferation in the positive direction and suppresses apoptosis. No report has described growth hormone (GH)-induced structural luteolysis. The present studies showed that GH induced structural luteolysis in rats after the induction of functional luteolysis by treatment with bromocriptine, and that apoptotic cells were present among luteal cells during structural luteolysis as shown by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling. Zymography showed that the activity of matrix metalloproteinase (MMP)-2 increased during GH-induced structural luteolysis. The expression of c-myc protein of luteal cells was significantly decreased, but proliferating cell nuclear antigens (PCNA) were conversely increased during structural luteolysis, as shown by Western blot analysis. We propose that an excessive increase in PCNA and a marked decrease in c-myc protein of luteal cells lead to a disorder in the signals concerned with DNA synthesis, causing mitotic catastrophe and inducing apoptosis in luteal cells, and that structural luteolysis may be triggered. GH-induced apoptosis in structural luteolysis therefore highly depends on the cell cycle. There are thought to be two mechanisms of GH-induced structural luteolysis. One is apoptosis, and the other is destruction of extracellular matrix by MMP.

Occurrence of Deoxyribonucleic Acid Fragmentation during Prolactin-Induced Structural Luteolysis in Cycling Rats1

We determined whether fragmentation of genomic DNA, one of the hallmarks of apoptosis, occurs during structural luteolysis in cycling rats. Corpora lutea (CL) were collected from rats at each estrous cycle stage (1800 h), and fragmented DNA was extracted. Only CL from rats at the proestrous stage showed distinct DNA fragmentation. To determine the period of occurrence of DNA fragmentation, CL were collected at several points between 1200 h on the day of proestrus and 0600 h on the day of estrus. Distinct DNA fragmentation was observed from 1800 h (proestrus) to 2400 h (proestrus), and the extent was significantly lower at 0600 h (estrus). It is known that prolactin (PRL) induces structural luteolysis in rats. To examine the role of PRL in luteal DNA fragmentation, 2-bromo-alpha-ergocryptine (BE) was used to suppress the PRL surge on the day of proestrus. CL collected at 1800 h from BE-treated rats did not show distinct DNA fragmentation, and PRL injection offset the effect of BE. Histochemical analysis with a 3'-end labeling technique confirmed the occurrence of DNA fragmentation in luteal tissue. These results suggest that apoptotic cell death occurs during PRL-induced structural luteolysis.

Coordinated expression of tissue-type plasminogen activator and plasminogen activator inhibitor type 1 during corpus luteum formation and luteolysis in the adult pseudopregnant rat.

Proteolytic activity generated by the plasminogen activator (PA) system is associated with many biological processes. Using an adult pseudopregnant rat model, we have studied how two components of the PA system, tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor type 1 (PAI-1), are expressed temporally and spatially during different developmental stages of the corpus luteum (CL). Northern blot analysis, in situ hybridization, in situ zymography, and fibrin overlay were used to analyze the expression and distribution of tPA and PAI-1 messenger RNA (mRNA) as well as PA activity in CL of different ages. We demonstrated that during the luteinization period (approximately days 1-2), tPA mRNA was highly and evenly expressed in newly formed CL, whereas PAI-1 mRNA was mainly detected in the central part of the same CL. In accordance with these findings, proteolytic activity generated by tPA was detected in the outer region of newly formed CL by in situ zymography. During the luteotropic period (approximately days 3-10), tPA mRNA expression was very low. PAI-1 mRNA expression was also low, but increased on day 10. As expected, proteolytic activity was very low during this period. During functional luteolysis (days 13-14) and subsequent structural luteolysis, tPA mRNA was elevated. PAI-1 mRNA was also expressed during this period. Moreover, the net PA activity, as determined by fibrin overlay, was relatively high during this period. Our studies indicate that tPA and PAI-1 are coordinately expressed in the CL, resulting in increased proteolytic activities during the luteinization and luteolytic periods. PA-mediated proteolysis may, therefore, play a role in both CL formation and luteolysis in rats.

Studies of the mechanism of action of prostaglandin F 2α induced luteolysis in rats

The effects of prostaglandin F 2α (PGF 2α administration on the utilization of low density lipoprotein (LDL) and progesterone secretion were examined in dispersed luteal cells from rat ovaries. Immature rats were rendered pseudopregnant with administration of pregnant mare serum gonadotropin and human chorionic gonadotropin. Animals were sacrificed at different times after PGF 2α (5 mg/kg) or vehicle administration on day-5 of pseudopregnancy. Administration of PGF 2α in vivo decreased human chorionic gonadotropin (hCG) binding to luteal cell membranes in vitro but enhanced binding of LDL. Utilization of labelled cholesterol for steroid synthesis from reconstituted LDL [( 3H)-CL-LDL] by dispersed luteal cells was enhanced following PGF 2α administration. This suggests that the LDL pathway is not suppressed during prostaglandin induced luteolysis. Progesterone and total progestin secretion in response to N 6-2′-0-Dibutyryladenosine 3′5′-cyclic monophosphate (cAMP) was decreased at 2,4 and 24 hours following PGF 2α administration demonstrating a post-cAMP defect i steroidogenesis. Addition of the hydroxylated sterols, 20 or 25-OH cholesterol as substrate stimulated progesterone secretion in vehicle treated rats in a dose dependent fashion with 20-OH cholesterol being more potent. Progesterone secretion in response to stimulation with luteinizing hormone (LH) and cAMP from vehicle treated rats was less than that observed with 20 or 25-OH cholesterol, indicating that endogeneous susbtrate may be a limiting factor in steroid synthesis. The maximal capacity of luteal tissue to produced progestins following PGF 2α administration was determined with 20-OH cholesterol as the substrate. The results suggest that the post-cAMP defect at 4 hours following PGF 2α administration may be due to failure of the cells to mobilize endogeneous cholesterol. However at 24 hours following PGF 2α administration the decreased ability of luteal cells to convert cholesterol to pregnenolone may contribute to decreased progesterone synthesis.

The relation between the effects of hysterectomy, decidual tissue, prolactin, or luteinizing hormone (LH) and the ability of indomethacin to prevent luteolysis in rats bearing LH-dependent corpora lutea.

In adult rats hysterectomized on day 8 of pseudopregnancy, the mean serum progesterone (P) level fell from 88 ng/ml on day 8 to 44 ng/ml on day 15 (n = 61). In response to a single sc injection of 0.5 ml of a specific antiserum to LH (LHAS) on day 10, the P level fell to less than 10 by day 15 in 29 of 33 rats; however, this fall, which was indicative of luteolysis, was briefly interrupted by a return to the control level 36 h after treatment. Indomethacin (400 micrograms, sc) administered 12 h before, during, and 12 h after the LHAS injection prevented the luteolysis that followed the 36 h surge in 10 of 15 rats (P less than 0.001). Treatment with 400 micrograms 2Br-alpha ergocryptine (CB 154), sc, on day 10, with or without indomethacin, however, induced a rapid, uninterrupted, and permanent fall to less than 10 in 13 of 13 rats. Treatment with both LHAS and CB 154 reduced the luteolytic effect of CB 154 (P less than 0.001), and indomethacin treatment combined with both LHAS and CB 154 tended to further reduce the luteolytic effect of CB 154 (P less than 0.01). Hypophysectomy on day 10, however, induced rapid, uninterrupted and permanent luteolysis in all rats (15); this was not affected by indomethacin (7 rats) or LHAS (8 rats). Pituitary homotransplantation on day 8 prevented the luteolytic effect of LHAS on day 10 in 6 of 6 rats (P less than 0.003). In decidual tissue (DT)-bearing rats, LHAS on day 10 induced rapid, uninterrupted, and permanent luteolysis in 18 of 18 rats. The response to LHAS on day 10 changed to that of the hysterectomized rat when the DT-bearing uterus was removed on day 8 (12 of 12 rats) or 10 (7 of 7 rats) (P less than 0.001), but did not change when it was removed on day 11 (5 of 5 rats). In DT-bearing rats hysterectomized on day 8, indomethacin in intrabursal Silastic wafers prevented luteolysis in response to LHAS on day 10 (6 of 6 rats; P less than 0.001). Intrabursal indomethacin had no effect on the response to LHAS in intact DT-bearing rats (3 of 3 rats). These results suggest that even when the corpus luteum becomes LH dependent, PRL may retard or prevent LHAS-induced luteolysis in hysterectomized rats. (ABSTRACT TRUNCATED AT 400 WORDS)

Prostaglandins in Hypothalamo-Pituitary and Ovarian Function

Some aspects of prostaglandin (PG) functions are reviewed including: 1) the role of PGs in the hypothalamic and pituitary control of gonadotropin secretions; and 2) their roles in ovulation, 3) in luteinization, and 4) in corpus luteum regression. PGE1 is known for its role in stimulation of increased cyclic adenosine 3',5' monophosphate (cAMP) and hormone secretion in the anterior pituitary. Direct effects of PGs on the secretion of luteinizing hormone, follicle stimulating hormone, and adrenal cortex hormones are not clearly known, but surmised. Such actions may not be the direct effects of PGs on pituitary action. Instead, more studies on receptor functions for PGs in pituitary cells are needed. Systemic administration of PGs has been shown to increase circulating levels of gonadotropins, adrenal cortex hormones, prolactin, follicle stimulating hormone, and luteinizing hormone; and in general, PGs of the E series are more potent than those of the F series. This response to systemic administration seems to be caused by an hypothalamic site of action, a conclusion based on several observations, including the observation that direct application of PGs to brain tissue causes a mimicking of endogenous PG effects of gonadotropin secretion. PGs also play a role in ovulation. Elevated PG levels in follicular tissues are induced by gonadotropins; cyclic nucleotides may be involved in mediating the action of gonadotropins on follicular PG production; a recognized time lag after exposure of the follicle to gonadotropin or cyclic nucleotides indicates that macromolecular synthesis may be involved in follicular PG production; and plasminogen activator may play a role in the process of follicular rupture that leads ot ovulation. The role of PGs in luteinization has been suggested by experiments which showed that granulosa cells cultured with PGE1 and PGE2 luteinized. PGs, particularly PGF2 alpha, cause luteal regression in many species, except perhaps in humans. And PGF2 alpha may be an antagonist of gonadotropin action in the corpus luteum. A proposed mechanism of PGF2 alpha-induced luteolysis in rats is also presented.

Prolactin and the regulation of 20alpha-dihydroprogesterone secretion of the super-luteinized rat ovary during luteolysis induced by a prostaglandin F2alpha analogue.

ABSTRACT Twenty-five day old female rats were treated with pregnant mare's serum gonadotrophin (PMSG) and human chorionic gonadotrophin (HCG) to achieve a state of luteinization. Eight days after the HCG administration luteolysis was induced by a subcutaneous injection of 5 μg of the prostaglandin F2α analogue cloprostenol (Estrumate®, ICI 80996). In animals treated with 2-Br-α-ergocryptine (BEC), administration of cloprostenol decreased serum progesterone levels from 580 to 20 ng/ml in 5 h and progesterone remained low for the next 18 h. The serum levels of 20α-dihydroprogesterone (20α-DHP) and prolactin (PRL) remained at pre-treatment values (20α-DHP 85 to 170 ng/ml; PRL less than 5 ng/ml) throughout the observation period. When animals treated with both BEC and cloprostenol were given PRL 5 h after the prostaglandin injection, an increased 20α-DHP level (630 ng/ml) was found 23 h after the cloprostenol administration, while the progesterone level was decreased (70 ng/ml). These findings were similar to the observations following cloprostenol treatment alone. The study indicates a causal relationship between the increase in the serum levels of PRL and 20α-DHP observed after PGF2α induced luteolysis in rats with superluteinized ovaries.

FAILURE OF CLOMIPHENE TO INTERRUPT GESTATION IN RATS TREATED WITH RESERPINE

Injections of clomiphene (3\m=.\0mg/kg) on Days 12, 14, 16 and 18 of pregnancy induced complete resorption of fetuses, a polyfollicular state of the ovary and luteolysis in rats. If reserpine was given at the same time as clomiphene, pregnancy was maintained and the status of the fetuses, placentae, ovaries and corpora lutea resembled that found in control rats. The fetal survival rate (96\m=.\7%)was found to be almost identical with that of the controls (97\m=.\9%).It is suggested that abnormal stimulation of the pituitary FSH and LH may possibly be the primary cause of the clomiphene-induced interruption of pregnancy in

Aspirin and the reversal of antifertility effect of iproniazid in rats

Iproniazid, a specific monoamine oxidase inhibitor which is known to exert its primary influence by interfering in the metabolism of catecholamines, showed its antifertility efficacy by causing luteolysis in rats. A concomitant regimen of iproniazid and aspirin, a very potent inhibitor of prostaglandin biosynthesis and release, consistently prevented the iproniazid-induced luteolysis and embryonic resorption in the test animals. It has been proposed that iproniazid-induced luteolysis in rats is probably mediated through an increased production of endogenous prostaglandins as a result of an abnormally higher concentration of catecholamines both at central and peripheral levels.

Association between pregnant mare serum-induced ovulation and luteolysis in rats and its dissociation by progesterone treatment.

In this study a dissociation of the ovulation-inducing action of pregnant mare serum gonadotropin (PMS) from the luteolytic action in rats is reported. The ability of prolactin and progesterone to inhibit ovulation was utilized to investigate the relationship between ovulation and luteolysis. The first estrus and ovulation were synchronized in 27-day-old prepubertal rats by the subcutaneous administration of 4 IU of PMS. Pseudopregnancy was induced by the subcutaneous administration of prolactin (100 mcg) beginning on the day of ovulation (Day 0) and maintained through Day 2. If prolactin therapy was discontinued on Day 2 a second injection of PMS on Day 3 resulted in ovulation accompanied by involution of the original corpora lutea. Continuous prolactin therapy from Day 0 through Day 6 not only prevented ovulation as a result of PMS administration on Day 3 but prevented luteolysis as well. Progesterone (8 mg/day) if administered on Days 3 through 6 inhibited ovulation in response to PMS administered on Day 3. It did not however prevent the luteolysis as a result of the ovulatory stimulus provided by PMS. Progesterone in the absence of PMS did not affect luteal weight. The dissociation of luteolysis from ovulation demonstrated that actual ovulation was not a requirement for luteolysis to occur but leaves open the possibility that an ovulatory stimulus may be an effective luteolytic stimulus.(AUTHORS MODIFIED)

Prolactin-induced luteolysis in rats following ovarian x-irradiation.

The relationship between the follicular elements of the ovary and prolactin—induced luteolysis was investigated in PMS—synchronized, immature rats whose ovaries had been subjected to 2500 rads of X—irradiation. Luteolysis was not observed in sham—irradiated rats or in x—irradiated rats receiving prolactin continuously (100 μg twice daily) from the day of ovulation until autopsy 12 days later. However, when prolactin administration was stopped for a 96–hr period between day 3 and day 6 and resumed on day 7, significantly (p < 0.01) smaller corpora lutea were observed after 5 successive days of prolactin administration when compared to irradiated rats receiving continuous prolactin. The interrupted prolactin regime, which successfully induced luteolysis when bilateral irradiation was carried out, failed to induce luteolysis in unilaterally x—irradiated rats. Prolactin—induced luteolysis in bilaterally x—irradiated rats was prevented by the administration of 1.0 μg of estradiol—17² per day between the time o...