Failure of two progesterone antagonists, mifepristone and onapristone, to affect luteal activity in lactating rats

Schoot, P. van der; Uilenbroek, J. Th. J.; Slappendel, Els

doi:10.1530/jrf.0.0870593

Cited by 12 publications

(13 citation statements)

References 17 publications

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“…Otherwise, a large decrease in both the number of steroidogenic cells and the CL volume was found in lactating rats on Day 10. This agrees with previous studies indicating that long-term regression of the CLP during lactation is dependent on PRL concentrations [18,33]. The absence of PRL surges in LHRHa-treated rats was also evidenced by the lack of structural luteolysis in the CL of the postpartum ovulation on Days 5 and 10 postpartum.…”

Section: Discussionsupporting

confidence: 92%

“…In studies focused on the regression of the CL of pregnancy (CLP) [14], it has been reported that more than 50% of luteal cells undergo apoptosis on Day 3 postpartum. Nevertheless, such a high rate of apoptosis would eliminate the totality of luteal cells shortly after parturition, which is in contrast to previous studies [18] indicating the presence of regressing CLP at advanced stages of lactancy, several weeks after parturition.…”

Section: Introductioncontrasting

confidence: 94%

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Luteolytic Effect of Prolactin Is Dependent on the Degree of Differentiation of Luteal Cells in the Rat1

Gaytán¹,

Bellido²,

Morales³

et al. 2001

Biology of Reproduction

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We studied the morphological and quantitative changes in cyclic corpora lutea (CCL) and in CL of pregnancy (CLP) during structural luteolysis. Elimination of CCL takes several cycles, and cell death occurs as successive apoptotic bursts, from 2100 h in proestrus to 1300 h in estrus. Each apoptotic burst determined a 60% decrease in the CL volume and an 80% decrease in the number of steroidogenic cells (SC). All these changes were inhibited by blocking the preovulatory prolactin (PRL) surge with bromocryptine (CB154). Neither apoptotic cells nor changes in the number of SC were found in regressing CLP from Day 21 of pregnancy to Day 2 postpartum, although there was a 50% decrease in the CLP volume and a 30% decrease in the mean cross-sectional area of SC. Treatment with CB154 on the day of parturition did not modify these regressive changes. On Day 5 postpartum, the volume of the CLP and the number of SC were equivalent in lactating rats (showing high PRL concentrations induced by pup suckling) and nonlactating noncycling rats (in which cyclicity and, therefore PRL surges, were blocked by treatment with LHRH antagonist). However, on Day 10 postpartum, the CLP volume and the number of SC were significantly decreased in lactating rats, and apoptotic cells were frequent. In postpartum cycling rats, the CLP did not show apoptotic cells on the day of the second postpartum estrus (on Day 5 postpartum), whereas on the day of the third postpartum estrus (on Day 9 postpartum), apoptotic cells were abundant. These results indicate that PRL does not induce apoptosis in the CLP before Day 5 postpartum and strongly suggest that the proapoptotic effect of PRL is dependent on the degree of differentiation of luteal cells.

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Section: Discussionsupporting

confidence: 92%

Section: Introductioncontrasting

confidence: 94%

Luteolytic Effect of Prolactin Is Dependent on the Degree of Differentiation of Luteal Cells in the Rat1

Gaytán¹,

Bellido²,

Morales³

et al. 2001

Biology of Reproduction

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“…While all pregnant rats were used for the study of the corpora lutea of pregnancy, only rats delivering on Day 23 and ovulating the next day [15,16] were used for the study of corpora lutea during lactation. Day of parturition was assigned as Day 0 of lactation [17]. On the day after parturition, litters were adjusted to 10 pups.…”

Section: Animal Preparation and Sample Collectionmentioning

confidence: 99%

“…During pregnancy, CL could be easily recognized macroscopically as large, reddish structures [17]: these are the functional corpora lutea of pregnancy (CLP).…”

Section: Dissection and Collection Of Corpora Luteamentioning

confidence: 99%

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Changes in the Proteome of Functional and Regressing Corpus Luteum During Pregnancy and Lactation in the Rat1

González-Fernández¹,

Martı́nez-Galisteo²,

Gaytán³

et al. 2008

Biology of Reproduction

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The corpus luteum (CL) is an exquisitely regulated transitory endocrine gland necessary for the onset and maintenance of pregnancy in mammals. Most of the data on the mechanisms of CL differentiation at the molecular level come from genomic studies, but direct protein data are scarce. Here we have undertaken a differential expression proteomic approach to identify, in an unbiased way, those proteins whose levels change significantly in the rat CL as it evolves from functionality during pregnancy to regression after parturition. Moreover, we have compared the regressing CL with the newly formed functional CL that coexist during lactation under the same endocrine environment. We have defined a "proteomic signature" of CL functionality, which is constituted by a set of 24 proteins with a few differences between pregnancy and lactation. Most of these markers are new and are involved in microtubule assembly, retinoic acid transport, and Raf kinase signaling cascade; 10 are enzymes that define a ketogenic metabolic landscape, demonstrating, for the first time, the prevalence of de novo cholesterol synthesis in luteal cells. The "proteomic signature of regression," on the other hand, is composed of nine proteins, one of which is 20alpha-hydroxysteroid dehydrogenase and two, ferritin and gamma-actin, are new. The discovery of unpredictable new actors in the differentiation process of CL reported here will contribute to new hypotheses that explain the complex female reproductive function at the protein level. It will also open new doors to research on each identified protein by relating them to cellular differentiation.

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Antiprogestagen RU486 prevents the LH-dependent decrease in the serum concentrations of inhibin in the rat

et al. 1996

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1. In the rat, the LH-dependent ovarian progesterone rise mediates several actions of the primary surge of LH on the ovary. This experiment was aimed at elucidating the effects of the antiprogestagen RU486 on the LH-dependent decrease in both the serum concentrations and the ovarian content of inhibin. 2. All rats in this experiment were treated with an antagonist of LHRH (1 mg/200 microliters saline at 0800 h in proestrus) to suppress the endogenous release of LH. One group of rats received 32 micrograms LH/250 microliters saline at 1200 h in proestrus. Other group was given 4 mg RU486/200 microliters oil at 0800 h in proestrus. The third group was injected with both RU486 and LH. Rats from the control group were injected with 250 microliters saline and 200 microliters oil. Animals were decapitated at 1700 h in proestrus and trunk blood and ovaries collected to determine the serum concentrations of LH, FSH, progesterone, 17 beta-estradiol and inhibin as well as the ovarian content of inhibin. 3. The ovulatory dose of LH in LHRHa-treated rats decreased both the serum concentrations and the ovarian content of inhibin and increased the serum concentrations of FSH. The administration of RU486 blocked the effect of LH on the serum concentrations of inhibin but not that on the ovarian content of inhibin. 4. Since the antiprogestagen RU486 blocked the effect of LH on the serum concentrations of inhibin, we conclude that ovarian progesterone, besides mediating the effects of the primary LH surge on the ovulatory process and luteinization, participates in the LH-dependent drop in the serum concentrations of inhibin in proestrous afternoon.

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Failure of two progesterone antagonists, mifepristone and onapristone, to affect luteal activity in lactating rats

Cited by 12 publications

References 17 publications

Luteolytic Effect of Prolactin Is Dependent on the Degree of Differentiation of Luteal Cells in the Rat1

Luteolytic Effect of Prolactin Is Dependent on the Degree of Differentiation of Luteal Cells in the Rat1

Changes in the Proteome of Functional and Regressing Corpus Luteum During Pregnancy and Lactation in the Rat1

Antiprogestagen RU486 prevents the LH-dependent decrease in the serum concentrations of inhibin in the rat

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