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PubMed2002

Involvement of endothelin-1 and its receptors in PGF2alpha-induced luteolysis in the rat.

The possible mediatory role of endothelin-1 (ET-1) in prostaglandin F(2alpha) (PGF(2alpha))-induced luteolysis in the rat was examined. The effect of PGF(2alpha) was tested on day 9 of pregnancy either in vivo, by injecting cloprostenol, an analog of PGF(2alpha) or in vitro, in isolated intact corpora lutea incubated with PGF(2alpha). Luteolysis was confirmed by progesterone determination in the peripheral blood serum or in the culture medium, respectively. Administration of cloprostenol (.0025 mg/rat) induced within 1 hr, a significant fall (from 56.8 to 27.6 ng/ml, P < 0.0001) in serum progesterone concentrations that was associated with an increased expression of the mRNA to ET-1 and its protein product in rat luteal tissue. Elevated level of ET-1 were also determined at the spontaneous regression of the CL, upon parturition. Expression of the ET receptors, ETA and ETB was not affected by cloprostenol. On the other hand, this PGF(2alpha) analog induced expression of luteal VEGF mRNA. In vitro experiments demonstrate that the LH (100 ng/ml)-induced increase in luteal progesterone secretion was reduced by PGF(2alpha) (1 microg/ml). The inhibitory effect of PGF(2alpha) was reversed by BQ123 (10(- 7) M), that is a selective ETA receptor antagonist. We conclude that the PGF(2alpha)-induced elevation in luteal expression of ET-1 combined with the reversal of its luteolytic effect by an ETA receptor antagonist suggest that ET-1 may take part in the PGF(2alpha)-induced luteolysis in the rat.

Animals↗
PubMed1985

Effects of luteinizing hormone-releasing hormone agonist and calcium upon adenylyl cyclase activity of human corpus luteum membranes.

We have investigated the ability of the agonist analog of luteinizing hormone-releasing hormone (LH-RH), D-Trp6-LH-RH (LH-RHa), and of CaCl2 to inhibit directly gonadotropin stimulation of adenylyl cyclase in a cell-free system prepared from human corpus luteum. In the presence of a submaximally effective concentration of hCG, addition of 10(-5)M final concentration of LH-RHa did not alter the gonadotropin-stimulated enzyme activity, nor did LH-RHa alone show any effect upon basal levels of the enzyme. The failure to inhibit adenylyl cyclase would indicate that the LH-RHa does not affect gonadotropin receptor binding or cAMP synthesis and/or degradation in this membrane system, suggesting that the luteolytic effects of LH-RH are unlikely to involve a direct antigonadotropic activity at the level of the human corpus luteum. In great contrast to LH-RHa, addition of CaCl2 resulted in a dose-dependent inhibition of hCG-stimulable adenylyl cyclase. Thus, in the presence of either a maximally or submaximally effective concentration of hCG, inhibition was significant at 0.5 mM CaCl2 added in excess of ATP (2 mM) and EDTA (1 mM), being about 90% upon addition of 2.5 mM CaCl2. We also found that calcium reduced enzyme stimulation by forskolin and the GTP analog, guanyl 5'-yl imidodiphosphate [GMP-P(NH)P] in a dose-related manner and that activation by NaF was less sensitive to inhibition by calcium. Accordingly, at 2.5 mM CaCl2, guanyl nucleotide and forskolin stimulations were inhibited 96% and 86%, respectively, while NaF stimulation was reduced by 40%. Because previous studies have shown that calcium does not impair gonadotropin binding activity, the calcium-dependent inhibition of gonadotropin responsiveness reported here would imply an alteration in the functional coupling of the components of the luteal adenylyl cyclase system. These data suggest that calcium may play a role in the regulation of gonadotropin action in the human corpus luteum.

Adenylyl Cyclases↗
PubMed1997

Prostaglandin F2alpha induces expression of prostaglandin G/H synthase-2 in the ovine corpus luteum: a potential positive feedback loop during luteolysis.

The primary role of prostaglandin (PG) F2alpha in regression of the corpus luteum has been clearly demonstrated in many mammalian species. We have used in vivo and in vitro approaches to investigate the possibility that exogenous PGF2alpha induces expression of prostaglandin G/H synthase-2 (PGHS-2; cyclooxygenase-2) and causes production of PGF2alpha in ovine luteal cells. Ewes received infusions into the ovarian artery of 1 ml PGF2alpha (1 micromol) or saline, and corpora lutea were collected at various times and analyzed for PGHS-2 mRNA using quantitative, competitive reverse transcription polymerase chain reaction. PGF2alpha dramatically increased the steady-state concentration of mRNA for PGHS-2 within 1 h, but basal concentration returned at 12 h posttreatment. In vitro studies using isolated ovine large luteal cells indicated that mRNA for PGHS-2 was induced by PGF2alpha, phorbol didecanoate, and ionomycin in a pattern similar to that observed in vivo. PGHS-2 protein was induced by all three treatments 4-12 h later, and accumulation of PGF2alpha in the culture media increased at 12 and 24 h posttreatment. In conclusion, we have provided evidence that PGF2alpha, probably acting through the protein kinase C/free intracellular calcium pathway, can stimulate large luteal cells to express PGHS-2 and produce PGF2alpha. This luteal PGF2alpha is likely to have an autocrine/paracrine function to augment the luteolytic effect of PGF2alpha of uterine origin.

Animals↗
PubMed1990

Variability in the developmental toxicity of bropirimine with the day of administration.

The aim of this study was to determine the mechanism by which bropirimine exerts its developmental toxicity. This drug is an immunomodulator and interferon inducer with antiviral and antitumor activities in experimental models. Timed-pregnant Upj:TUC(SD)spf (Sprague-Dawley) rats were given a single oral (gastric intubation) dose of bropirimine at 200 or 400 mg/kg (doses as high as 100 mg/kg/day have been employed in human cancer trials) on days 5, 6, 7, 8, 9, 10, 11, or 12 of gestation and in a second experiment on day 12, 13, 14, 15, 16, 17, 18, or 19 of gestation. The dams were killed 24 hours after dosing and their uterine contents examined. In a third experiment, bropirimine (400 mg/kg) was administered on day 4 of gestation and the uteri of different groups were examined on day 8, 9, 10, 11, or 12 of gestation. Serum progesterone levels were measured at sacrifice. In the first two experiments a battery of hematologic/clinical chemistry assays also were performed. In all three experiments, bropirimine-related maternal toxicity was observed; such toxicity was characterized by significant decreases in weight gain, relative to the concurrent vehicle controls, as well as significant differences in several blood parameters including platelets, white blood cells, alanine aminotransferase, and aspartate transaminase. In the first experiment, bropirimine treatment on day 11, but not day 12, resulted in significant decreases in the mean number of live embryos per litter. In the second experiment, significant decreases in the number of live fetuses per litter occurred 24 hours after dosing on day 18 (200 and 400 mg/kg groups) or day 19 (400 mg/kg group). Decreases in serum progesterone appeared to correlate well with the embryolethal effects seen after treatment between days 6 and 11 of gestation, but not with the fetal lethality seen when treatment was given on day 17 or 18. The decreases in serum progesterone levels found most likely were the result of a luteolytic effect, although it is unknown if bropirimine has a direct or indirect effect on the corpora lutea. In the third experiment, bropirimine treatment on day 4 of gestation resulted in only slight preimplantational losses, but significant decreases were found in mean number of live embryos per litter after day 9. Uterine decidual necrosis has been observed in the first experiment where bropirimine was given on day 11; however, treatment on day 4 resulted in an apparent decrease in decidual development but not necrosis.

Animals↗
PubMed2000

Prostaglandin metabolism in the ovine corpus luteum: catabolism of prostaglandin F(2alpha) (PGF(2alpha)) coincides with resistance of the corpus luteum to PGF(2alpha).

To examine possible mechanisms involved in resistance of the ovine corpus luteum to the luteolytic activity of prostaglandin (PG)F(2alpha), the enzymatic activity of 15-hydroxyprostaglandin dehydrogenase (PGDH) and the quantity of mRNA encoding PGDH and cyclooxygenase (COX-2) were determined in ovine corpora lutea on Days 4 and 13 of the estrous cycle and Day 13 of pregnancy. The corpus luteum is resistant to the action of PGF(2alpha) on Days 4 of the estrous cycle and 13 of pregnancy while on Day 13 of the estrous cycle the corpus luteum is sensitive to the actions PGF(2alpha). Enzymatic activity of PGDH, measured by rate of conversion of PGF(2alpha) to PGFM, was greater in corpora lutea on Day 4 of the estrous cycle (P < 0.05) and Day 13 of pregnancy (P < 0.05) than on Day 13 of the estrous cycle. Levels of mRNA encoding PGDH were also greater in corpora lutea on Day 4 of the estrous cycle (P < 0. 01) and Day 13 of pregnancy (P < 0.01) than on Day 13 of the estrous cycle. Thus, during the early estrous cycle and early pregnancy, the corpus luteum has a greater capacity to catabolize PGF, which may play a role in the resistance of the corpus luteum to the actions of this hormone. Levels of mRNA encoding COX-2 were undetectable in corpora lutea collected on Day 13 of the estrous cycle but were 11 +/- 4 and 44 +/- 28 amol/microgram poly(A)(+) RNA in corpora lutea collected on Day 4 of the estrous cycle and Day 13 of pregnancy, respectively. These data suggest that there is a greater capacity to synthesize PGF(2alpha), early in the estrous cycle and early in pregnancy than on Day 13 of the estrous cycle. In conclusion, enzymatic activity of PGDH may play an important role in the mechanism involved in luteal resistance to the luteolytic effects of PGF(2alpha).

Animals↗
PubMed1985

Ectopic pituitary grafts in mice: hormone levels, effects on fertility, and the development of adenomyosis uteri, prolactinomas, and mammary carcinomas.

Some endocrinological consequences of grafting hypophyses of mice to sites distant from the hypothalamic-pituitary portal vessels were investigated. Serum PRL levels in recipients rose within 3 weeks to levels seen during pregnancy, resulting in a premature increase in serum progesterone (P) levels. After 7 weeks, luteolytic effects were evident in BALB/c females, and P values had plateaued in the range of those seen in normal adult animals, while in BALB/c X C3H F1 hybrids, this effect was delayed, and P values rose, reaching, in some animals, levels reported during pregnancy. Despite continuing hyperprolactinemia, the fertility of graft-bearing females was reduced only slightly. By the 6th month, lesions of adenomyosis were frequent in uteri of C3H and F1 hybrids, but essentially absent from BALB/c animals. The number of corpora lutea was reduced in all experimental groups, yet serum P values were somewhat elevated in hybrid females and BALB/c animals bearing three grafts. Evidence is presented indicating that PRL enhances the action of P on both the estrogen-stimulating vagina and uterus. Small groups of grafted BALB/c and hybrid females not infected with exogenous mouse mammary tumor virus were allowed to survive until mammary cancers developed or until they reached 18 months of age. The grafts in the hybrids routinely became adenomatous, producing serm PRL levels of 1-21 X 10(3) ng/ml; only one secreted excessive GH. Adenomyosis wained in the aged hybrids, apparently due to declining ovarian function. The majority of the animals developed adenoid cystic mammary cancers that seemed to arise from areas of hyperplasia within dilated ducts rather than from alveolar hyperplasias, as is most frequently the case in mice carrying exogenous mouse mammary tumor virus.

Aging↗
PubMed1993

Termination of early pregnancy in sheep with dinoprost or cloprostenol: comparison of two commercial preparations.

The response of the ovine corpus luteum of pregnancy to the luteolytic effect of prostaglandin F2 alpha (dinoprost) and its analogue, cloprostenol, was tested in both superovulated and untreated ewes by monitoring plasma progesterone concentrations at the time of 'material recognition' and beyond (days 13 to 30). On days 13, 16 and 28, the majority of the superovulated ewes were refractory to 10 mg of dinoprost. The luteolytic efficacy of 250 micrograms of cloprostenol was compared with 10 mg of dinoprost on day 20 of pregnancy in superovulated and untreated animals and the two prostaglandins were also compared on days 26 and 30 in animals previously unresponsive to dinoprost. Generally, cloprostenol was more effective than dinoprost because there was less refractoriness on day 20 and no refractoriness on days 26 and 30 to this prostaglandin. No difference in the sensitivity to this drug was found between the superovulated and untreated groups on days 20 and 26.

Abortion, Induced↗
PubMed1980

Effects of prostaglandins on peripheral progesterone and uterine diamine oxidase in the pregnant hamster.

Serum progesterone and uterine levels of diamine oxidase (DAO) activity were determined during pregnancy in hamsters. Progesterone was elevated on Day 1 of pregnancy, had a transient peak on Day 5, remained relatively constant on Days 6-10, and then increased on Days 13 and 14. Uterine DAO activity could not be detected until Day 7 of pregnancy approximately 1 1/2 days after the initiation implantation. DAO activity was associated with placental tissue, and more than 90% of the activity was localized in the maternal placenta. The temporal relationship between changes in serum concentrations of progesterone and uterine levels of DAO activity following PG administration also was studied. Serum progesterone was significantly depressed by 6 hr after treatment with PGs on Day 7 of pregnancy. However, uterine levels of DAO activity at 6 hr in the treated animals were not different from those in control animals. In contrast, both the serum progesterone concentrations and uterine levels of DAO activity were significantly lower at 24 hr after PG treatment. The effects of PG treatment on uterine DAO activity were completely blocked by concomitant administration of progesterone. However, concomitant administration of Provera only blocked the effect of one PG analog that was tested (9-deoxo-9-methylene-16,16-dimethyl-PGE2). The data indicate that changes in uterine DAO activity following treatment with the PGs used here are primarily a consequence of a decrease in peripheral progesterone (i.e. a luteolytic effect of the PG).

Amine Oxidase (Copper-Containing)↗
PubMed1988

Effects of Tokishakuyakusan and its components on rat corpus luteum function in vitro.

27-day-old female rats received 20 IU PMS and 56 hours later, 40 IU hCG. Seven days after hCG treatment, the resected ovaries were perifused with NIH-LH, Tokishakuyakusan (TJ-23) or its components. LH and TJ-23 increased progesterone in media and LH was more effective than TJ-23. Hoelen, Peony root, Alisma rhizome and Japanese angelica root also augmented progesterone. 17 alpha-hydroxyprogesterone and 20 alpha-hydroxyprogesterone were not stimulated by TJ-23. These results suggest that TJ-23 stimulates corpora lutea to secrete progesterone without direct luteotropic or luteolytic effect and that the effect may be attributable to Hoelen, Peony root, Alisma rhizome or Japanese angelica root.

Animals↗
PubMed1979

Clinical effects of orally administered extracts of Montanoa tomentosa in early human pregnancy.

Freshly prepared aqueous decocts of the Mexican plant Montanoa tomentosa (Zoapatle) were administered orally to six women in the early stages of pregnancy for two days prior to the interruption of gestation by vacuum aspiration. The daily dose administered varied between 1.0 and 1.4 gm-equivalent of dry leaves per kilogram of body weight. A comparable control group of six pregnant women received the same volume of commercial tea according to the same schedule before vacuum aspiration. Administration of Zoapatle extracts resulted in a menstrual-like cramp and a significant dilatation of the cervix in all subjects studied. In four of the six subjects the menstrual-like pains were associated with bleeding. No comparable effects were observed in the control group. Peroral administration of Zoapatle decocts did not produce any cardiovascular changes, and it did not influence the hematologic status, liver, kidney, and thyroid function, blood lipids, proteins, and electrolyte status. Under the experimental conditions used, Zoapatle extracts did not induce a luteolytic effect judged from the plasma progesterone (and estradiol) levels. It is concluded that peroral administration of freshly prepared decocts of Zoapatle in early pregnancy exerts a distinct uterotonic effect and induces cervical dilatation and uterine bleeding. These changes are not associated with any effect on the plasma levels of progesterone and estradiol or with any untoward side effects.

Abortifacient Agents↗
PubMed2005

Changes in steady-state concentrations of messenger ribonucleic acids in luteal tissue during prostaglandin F2alpha induced luteolysis in mares.

Transvaginal ultrasound-guided luteal biopsy was used to evaluate the effects of prostaglandin (PG)F2alpha on steady-state concentrations of mRNA for specific genes that may be involved in regression of the corpus luteum (CL). Eight days after ovulation (Hour 0), mares (n=8/group) were randomized into three groups: control (no treatment or biopsy), saline+biopsy (saline treatment at Hour 0 and luteal biopsy at Hour 12), or PGF2alpha+biopsy (5mg PGF2alpha at Hour 0 and luteal biopsy at Hour 12). The effects of biopsy on CL were compared between the controls (no biopsy) and saline+biopsy group. At Hour 24 (12h after biopsy) there was a decrease in circulating progesterone in saline group to 56% of pre-biopsy values, indicating an effect of biopsy on luteal function. Mean plasma progesterone concentrations were lower (P<0.001) at Hour 12 in the PG group compared to the other two groups. The relative concentrations of mRNA for different genes in luteal tissue at Hour 12 was quantified by real time PCR. Compared to saline-treated mares, treatment with PGF2alpha increased mRNA for cyclooxygenase-2 (Cox-2, 310%, P<0.006), but decreased mRNA for LH receptor to 44% (P<0.05), steroidogenic acute regulatory protein to 22% (P<0.001), and aromatase to 43% (P<0.1) of controls. There was no difference in mRNA levels for PGF2alpha receptor between PG and saline-treated groups. Results indicated that luteal biopsy alters subsequent luteal function. However, the biopsy approach was effective for collecting CL tissue for demonstrating dynamic changes in steady-state levels of mRNAs during PGF2alpha-induced luteolysis. Increased Cox-2 mRNA concentrations suggested that exogenous PGF2alpha induced the synthesis of intraluteal PGF2alpha. Thus, the findings are consistent with the concept that an intraluteal autocrine loop augments the luteolytic effect of uterine PGF2alpha in mares.

Animals↗
PubMed1978

Interceptive activity of azastene in rhesus monkeys.

Azastene is an orally effective "luteolytic" agent in rhesus monkeys. In nonpregnant monkeys it reverses the human chorionic gonadotropin-stimulated increase in progesterone production and delay in the onset of menstruation, and, in inseminated monkeys, it prevents pregnancy if given for 5 days beginning on day 24 of the menstrual cycle. The drug is also effective in terminating pregnancy if given for 5 days beginning on approximately day 26, day 50, or day 80 of gestation. Concurrent progesterone administration prevents the interceptive action of the drug. Although azastene inhibits gonadal and placental progesterone production, it has no effect on cortisol production in monkeys and is devoid of apparent hormonal activity.

Abortifacient Agents↗
PubMed1994

Prostaglandin F2 alpha stimulates release of insulin-like growth factor binding protein-3 from cultured human granulosa-luteal cells.

Human ovarian follicular fluid contains a number of insulin-like growth factor binding proteins (IGFBP) of which IGFBP-3 is the most abundant. IGFBP-3 synthesis is growth hormone-regulated. We studied the effect of prostaglandin F2 alpha (PGF2 alpha) on IGFBP-3 secretion by cultured human granulosa-luteal cells from follicular aspirates of women participating in an in-vitro fertilization programme. The IGFBP-3 concentration was measured using a specific monoclonal immunofluorimetric assay. Contrary to a previous report on unstimulated follicles, this study demonstrated a positive correlation between follicular fluid IGFBP-3 concentration and follicular size. PGF2 alpha was found to stimulate in a dose-dependent fashion the secretion of IGFBP-3. Significant (P < 0.05) effects were found at PGF2 alpha concentrations of 10(-8), 10(-7) and 10(-6) M. Because IGFBP-3 inhibits progesterone production stimulated by insulin-like growth factor (IGF)-I, the PGF2 alpha-induced stimulation of IGFBP-3 production may be one of the mechanisms whereby PGF2 alpha exerts its luteolytic effect via the IGF system.

Carrier Proteins↗
PubMed1986

Mechanism of action of prostaglandin F2 alpha-induced luteolysis: evidence for a rapid effect on the guanine nucleotide binding regulatory component of adenylate cyclase in rat luteal tissue.

The initial events in prostaglandin F2 alpha-(PGF2 alpha)-induced luteolysis were studied in pregnant mare serum gonadotropin/human chorionic gonadotropin-(PMSG/hCG)-treated rats with luteinized ovaries. Injection with a potent PGF2 alpha analog (cloprostenol, 5 micrograms/ml) induced functional luteolysis, as assessed by plasma levels of progesterone and 20 alpha-dihydroprogesterone. At 0.5 and 3 h after cloprostenol administration the luteolytic effect was also evident as a reduced response of luteal adenylate cyclase to all stimulatory agents tested, LH, isoproterenol, fluoride, guanylylimidodiphosphate and forskolin. 24 h after cloprostenol the response to all agents, except to LH, had returned to normal. This general and transient block of the luteal adenylate cyclase system indicates that a common factor, possibly the stimulatory guanine nucleotide binding protein (Ns), is involved in the mechanism of action of PGF2 alpha. To test this hypothesis, we measured the functional coupling of the Ns protein to the beta-adrenergic receptor in luteal membranes. Binding competition curves showed a marked shift to the right in membranes prepared from rats injected with cloprostenol 0.5 and 3 h before membrane preparation, while at 24 h after cloprostenol the shift had disappeared. The total number of beta-adrenergic receptors was, however, not affected by the cloprostenol treatment. Computer analysis of the data indicates that, at 0.5 and 3 h after cloprostenol treatment, there was a reduced number of high affinity binding sites, 38 and 41%, respectively, compared to 53% for control membranes. The cellular mechanism for this action of PGF2 alpha on the Ns protein remains to be elucidated.

Adenylyl Cyclases↗
PubMed1984

Effects on the oestrous cycle of dairy cows of the administration of colostrum in the mid-luteal phase.

A group of 13 cows were dosed orally nine or 10 days after a normal oestrous cycle; six animals received colostrum, five animals received milk containing varying amounts of oestrone sulphate, and two cows were given milk containing a low level of oestrone sulphate. Measurements of milk progesterone levels after dosing showed that colostrum had an apparent luteolytic effect, milk containing oestrone sulphate at a level of 2000 pg/ml had a less marked effect on milk progesterone and those animals receiving milk showed no reduction in milk progesterone. These results show that there is a physiological basis for the practice of inducing overt oestrus in cows showing no visible oestrus, by dosing them with colostrum.

Animals↗
PubMed1975

Influence of intrauterine saline infusion upon the oestrous cycle of the mare.

The effect of intrauterine saline on reproductive function was studied by infusion of mares in anoestrus, dioestrus, oestrus and prolonged dioestrus. Anoestrous mares were unaffected except near the beginning and end of the breeding season when anovulatory heats were induced. Dioestrous mares infused between Days 5 and 9 returned to heat an average of 3-8 days earlier than expected, and infusions during dioestrus were followed by ovulatory heats of normal fertility. Three mares in prolonged dioestrus showed ovulatory heats within 3 to 9 days of infusion. Infusions during oestrus had no appreciable effect. Repeated infusions were clinically harmless but post-infusion bacteriological swabs from the uterus were positive. In two cases studied, infusion was followed by a fall in peripheral plasma progestagen concentrations. Evidence was obtained that vaginal and cervical dilatation and oxytocin were not involved in the mechanisms and it is postulated that the luteolytic effect of intrauterine saline is mediated by prostaglandin.

Animals↗
PubMed2002

Old, new and the newest concepts of inhibition of luteolysis during early pregnancy in pig.

In 1977 Bazer and Thatcher proposed that maternal recognition of pregnancy in the pig involves the secretion of PGF(2alpha) towards the uterine lumen (exocrine) rather than towards the uterine venous drainage (endocrine) as occurs in the non-pregnant pig during the mid to late stages of the estrous cycle. The retrograde transfer of PGF(2alpha) from the venous blood and uterine lymph into the uterus and the ability of the uterine vein and artery wall to accumulate PGF(2alpha) could constitute a part of putative mechanism of corpus luteum protection during early pregnancy. A luteotropic/anti-luteolytic effect of PGE(2) in the pig also has been frequently demonstrated and it seems that the most effective agent in changing PGE(2):PGF(2alpha) secretion is estradiol. The role for oxytocin during luteolysis and early pregnancy is controversial. It appears, however, that the main function of this hormone is autocrine and/or paracrine stimulation of PGF(2alpha) secretion. Pig trophoblastic interferons, unlike those of ruminants, do not themselves exert an anti-luteolytic effect in pigs. It is likely, that cytokines and angiogenic growth factors are involved in the initiation of luteolysis and/or maintenance of corpora lutea (CL).A discovery of functional LH receptors in porcine endometrium opened a new possibility for this hormone in luteolysis and perhaps in recognition of pregnancy in pigs. The endogenous LH pulses can provoke prostaglandin secretion from endometrium in pigs. On the other hand prolongation of up-regulation of LH receptors in endometrium of early pregnant gilts can additionally increase angiogenic factor production before the process of implantation is completed. Finally new integrated concepts of luteolysis and inhibition of luteolysis in pigs based on selectively reviewed information are presented.

Animals↗
PubMed1999

Expression of the steroidogenic acute regulatory protein and luteinizing hormone receptor and their regulation by tumor necrosis factor alpha in rat corpora lutea.

Expression of both mRNA and protein of the steroidogenic acute regulatory protein (StAR), in correlation with progesterone (P) production and LH receptor (LHR) mRNA expression, was studied in the corpora lutea (CL) of gonadotropin-induced-pseudopregnant and pregnant rats at various stages of CL development. Immature female rats, 21-22 days old, were injected s.c. with 20 IU eCG to stimulate follicle growth and then with 20 IU hCG 48 h later to induce ovulation. The ovaries were removed at various stages of CL development; either CL were isolated and snap frozen for total RNA analysis, or whole ovaries were fixed in Bouin's fluid for paraffin sectioning. The results of in situ hybridization, immunohistochemistry, and Northern blotting showed that the increase in StAR mRNA and protein expression was well correlated with the increase in serum P concentration. StAR expression was restricted to the luteal cells or theca cells in antral follicles. Both StAR mRNA and protein in the CL of pseudopregnant rats increased steadily on Day 1 and Day 4, reached highest levels on Day 4, and then dropped sharply on Day 8 when luteolysis takes place. LHR mRNA content was high on Day 1 but dropped significantly on Day 2. LHR mRNA increased to high levels on Day 4 and 8 and then declined on Day 12. StAR mRNA and protein levels in the CL of pregnant rats were high during early luteal development (Day 2, 4), increased even further on Day 9, and decreased on Day 13 when luteolysis takes place. It is therefore suggested that the expression of StAR coincides well with the capacity of P production in the CL and that StAR expression can be used as a functional "marker" of CL development. To study the possible effect of cytokines on StAR expression, pseudopregnant rats on Day 5 were injected s.c. with 10 IU hCG plus 20 microg prolactin (PRL), with or without 500 IU tumor necrosis factor alpha (TNFalpha) 30 min later. TNFalpha significantly inhibited hCG/PRL-induced StAR and LHR mRNA expression at 1 and 3 h post-TNFalpha. It is suggested that the luteolytic effect of TNFalpha may be mediated by its direct inhibition on StAR expression or by an indirect decrease in LHR expression.

Animals↗