Effects of Deletion of the Prolactin Receptor on Ovarian Gene Expression

Overview

Journal Reprod Biol Endocrinol

Publisher Biomed Central

Specialties Endocrinology
Reproductive Medicine

Date 2003 Mar 21

PMID 12646063

Citations 35

Authors

Isabelle Grosdemouge

Anne Bachelot

Aurelie Lucas

Nathalie Baran

Paul A Kelly

Nadine Binart

Affiliations

Soon will be listed here.

Abstract

Prolactin (PRL) exerts pleiotropic physiological effects in various cells and tissues, and is mainly considered as a regulator of reproduction and cell growth. Null mutation of the PRL receptor (R) gene leads to female sterility due to a complete failure of embryo implantation. Pre-implantatory egg development, implantation and decidualization in the mouse appear to be dependent on ovarian rather than uterine PRLR expression, since progesterone replacement permits the rescue of normal implantation and early pregnancy. To better understand PRL receptor deficiency, we analyzed in detail ovarian and corpora lutea development of PRLR-/- females. The present study demonstrates that the ovulation rate is not different between PRLR+/+ and PRLR-/- mice. The corpus luteum is formed but an elevated level of apoptosis and extensive inhibition of angiogenesis occur during the luteal transition in the absence of prolactin signaling. These modifications lead to the decrease of LH receptor expression and consequently to a loss of the enzymatic cascades necessary to produce adequate levels of progesterone which are required for the maintenance of pregnancy.

Citing Articles

Elevated levels of exogenous prolactin promote inflammation at the maternal-fetal interface via the JAK2/STAT5B signaling axis.

Williams A, Hossack D, Thompson N, Sim Y, Wilson C, Schuch V Front Immunol. 2025; 15:1496610.

PMID: 39763651 PMC: 11701216. DOI: 10.3389/fimmu.2024.1496610.

Increased susceptibility to diet-induced obesity in female mice impairs ovarian steroidogenesis: The role of elevated leptin signalling on nodal activity inhibition in theca cells.

Wolodko K, Sentjurc T, Walewska E, Laniecka E, Jura M, Galvao A Mol Metab. 2024; 91():102062.

PMID: 39536822 PMC: 11646782. DOI: 10.1016/j.molmet.2024.102062.

IMPACT OF REAL-LIFE ENVIRONMENTAL EXPOSURES ON REPRODUCTION: Systemic and ovarian impacts of heat stress in the porcine model.

Keating A, Ross J, Baumgard L Reproduction. 2024; 168(6.

PMID: 39401133 PMC: 11623122. DOI: 10.1530/REP-24-0217.

Aberrant CD8T cells drive reproductive dysfunction in female mice with elevated IFN-γ levels.

Bafor E, Erwin-Cohen R, Martin T, Baker C, Kimmel A, Duverger O Front Immunol. 2024; 15:1368572.

PMID: 38698852 PMC: 11064017. DOI: 10.3389/fimmu.2024.1368572.

The association between serum prolactin levels and live birth rates in non-PCOS patients: A retrospective cohort study.

Xu X, Yang A, Han Y, Wang W, Hao G, Cui N PLoS One. 2023; 18(11):e0295071.

PMID: 38019871 PMC: 10686428. DOI: 10.1371/journal.pone.0295071.

References

Fero M, Rivkin M, Tasch M, Porter P, Carow C, Firpo E . A syndrome of multiorgan hyperplasia with features of gigantism, tumorigenesis, and female sterility in p27(Kip1)-deficient mice. Cell. 1996; 85(5):733-44. DOI: 10.1016/s0092-8674(00)81239-8. View

Moons D, Jirawatnotai S, Tsutsui T, Franks R, Parlow A, Hales D . Intact follicular maturation and defective luteal function in mice deficient for cyclin- dependent kinase-4. Endocrinology. 2002; 143(2):647-54. DOI: 10.1210/endo.143.2.8611. View

Matsuyama S, Chang K, Kanuka H, Ohnishi M, Ikeda A, Nishihara M . Occurrence of deoxyribonucleic acid fragmentation during prolactin-induced structural luteolysis in cycling rats. Biol Reprod. 1996; 54(6):1245-51. DOI: 10.1095/biolreprod54.6.1245. View

Sicinski P, Donaher J, Geng Y, Parker S, Gardner H, Park M . Cyclin D2 is an FSH-responsive gene involved in gonadal cell proliferation and oncogenesis. Nature. 1996; 384(6608):470-4. DOI: 10.1038/384470a0. View

Ormandy C, Camus A, Barra J, Damotte D, Lucas B, Buteau H . Null mutation of the prolactin receptor gene produces multiple reproductive defects in the mouse. Genes Dev. 1997; 11(2):167-78. DOI: 10.1101/gad.11.2.167. View

Kanuka H, Matsuyama S, Ohnishi M, Matsumoto Y, Nishihara M, Takahashi M . Prolactin expresses differential effects on apoptotic cell death of luteal cells in vivo and in vitro. Endocr J. 1997; 44(1):11-22. DOI: 10.1507/endocrj.44.11. View

Zhong L, Parmer T, Robertson M, Gibori G . Prolactin-mediated inhibition of 20alpha-hydroxysteroid dehydrogenase gene expression and the tyrosine kinase system. Biochem Biophys Res Commun. 1997; 235(3):587-92. DOI: 10.1006/bbrc.1997.6833. View

Gaytan F, Morales C, Bellido C, Aguilar E, Sanchez-Criado J . Role of prolactin in the regulation of macrophages and in the proliferative activity of vascular cells in newly formed and regressing rat corpora lutea. Biol Reprod. 1997; 57(2):478-86. DOI: 10.1095/biolreprod57.2.478. View

Horseman N, Zhao W, Tanaka M, Nakashima K, Engle S, Smith F . Defective mammopoiesis, but normal hematopoiesis, in mice with a targeted disruption of the prolactin gene. EMBO J. 1998; 16(23):6926-35. PMC: 1170296. DOI: 10.1093/emboj/16.23.6926. View

10.

Redmer D, Reynolds L . Angiogenesis in the ovary. Rev Reprod. 1996; 1(3):182-92. DOI: 10.1530/ror.0.0010182. View

11.

Arakane F, King S, Du Y, Kallen C, Walsh L, Watari H . Phosphorylation of steroidogenic acute regulatory protein (StAR) modulates its steroidogenic activity. J Biol Chem. 1998; 272(51):32656-62. DOI: 10.1074/jbc.272.51.32656. View

12.

Bole-Feysot C, Goffin V, Edery M, Binart N, Kelly P . Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice. Endocr Rev. 1998; 19(3):225-68. DOI: 10.1210/edrv.19.3.0334. View

13.

Teglund S, Mckay C, Schuetz E, Van Deursen J, Stravopodis D, Wang D . Stat5a and Stat5b proteins have essential and nonessential, or redundant, roles in cytokine responses. Cell. 1998; 93(5):841-50. DOI: 10.1016/s0092-8674(00)81444-0. View

14.

Robker R, Richards J . Hormone-induced proliferation and differentiation of granulosa cells: a coordinated balance of the cell cycle regulators cyclin D2 and p27Kip1. Mol Endocrinol. 1998; 12(7):924-40. DOI: 10.1210/mend.12.7.0138. View

15.

Tong W, Kiyokawa H, Soos T, Park M, Soares V, Manova K . The absence of p27Kip1, an inhibitor of G1 cyclin-dependent kinases, uncouples differentiation and growth arrest during the granulosa->luteal transition. Cell Growth Differ. 1998; 9(9):787-94. View

16.

Wandji S, Wood T, Crawford J, Levison S, Hammond J . Expression of mouse ovarian insulin growth factor system components during follicular development and atresia. Endocrinology. 1998; 139(12):5205-14. DOI: 10.1210/endo.139.12.6367. View

17.

Feltus F, Groner B, Melner M . Stat5-mediated regulation of the human type II 3beta-hydroxysteroid dehydrogenase/delta5-delta4 isomerase gene: activation by prolactin. Mol Endocrinol. 1999; 13(7):1084-93. DOI: 10.1210/mend.13.7.0314. View

18.

Trigatti B, Rayburn H, Vinals M, Braun A, Miettinen H, Penman M . Influence of the high density lipoprotein receptor SR-BI on reproductive and cardiovascular pathophysiology. Proc Natl Acad Sci U S A. 1999; 96(16):9322-7. PMC: 17781. DOI: 10.1073/pnas.96.16.9322. View

19.

Riedlinger G, Okagaki R, Wagner K, Rucker 3rd E, Oka T, Miyoshi K . Bcl-x is not required for maintenance of follicles and corpus luteum in the postnatal mouse ovary. Biol Reprod. 2002; 66(2):438-44. DOI: 10.1095/biolreprod66.2.438. View

20.

Niswender G, Juengel J, Silva P, Rollyson M, McIntush E . Mechanisms controlling the function and life span of the corpus luteum. Physiol Rev. 2000; 80(1):1-29. DOI: 10.1152/physrev.2000.80.1.1. View