Skip to main content

Advertisement

SpringerLink
Log in

Involvement of rat gonadotrope progesterone receptor in the ovary-mediated inhibitory action of FSH on LH synthesis

  • Original Paper
  • Published:
Journal of Physiology and Biochemistry Aims and scope Submit manuscript

Abstract

Rat ovaries stimulated with human follicle-stimulating hormone (hFSH) overexpress a factor that attenuates the LH surge in the rat: the putative gonadotropin surge-attenuating factor (GnSAF). A reduced gondadotrope progesterone receptor (PR) phosphorylation/activation is likely to be the main causative factor involved in GnSAF bioactivity on LH release. Besides, GnSAF reduces LH synthesis as well as LH secretion, and it is not known whether PR is involved in the inhibitory action of GnSAF on LH synthesis. Thus, the purpose of the present work was to evaluate the involvement of PR in the inhibitory effects of GnSAF on LH synthesis in cycling rats. To this end we used a specific radioimmunoassay and reverse transcription-polymerase chain reaction (RT-PCR) to study the effect on LH pituitary content and LHβ mRNA expression of PR occupancy with P (3 mg/0.2 ml oil in diestrus) on the inhibitory effects of hFSH (0, 0.1, 1, and 10 IU) in metestrus (day 2) and diestrus (day 3) on LH synthesis on proestrus in intact and on day 4 in day 2 ovariectomized (OVX) rats injected with 5 and 10 μg of estradiol benzoate (EB) on days 2 and 3, respectively. Results showed that (1) hFSH decreased pituitary LH content in intact, but not in OVX rats injected with EB, without affecting LHβ mRNA levels, and (2) PR occupancy with P annulled the inhibitory action of hFSH on pituitary LH content. These results indicate that PR is involved in ovarian GnSAF effect on LH content probably at a post-transcriptional level.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  PubMed  CAS  Google Scholar 

  2. Byrne B, Fowler PA, Templeton A (1996) Role of progesterone and nonsteroidal ovarian factors in regulating gonadotropin-releasing hormone self-priming in vitro. J Clin Endocrinol Metab 81:1454–1459

    Article  PubMed  CAS  Google Scholar 

  3. Cowking L, Fowler PA, Templeton A (1995) Acute exposure to ovarian steroids and a PKC activator do not overcome GnSAF bioactivity in vitro. J Reprod Fertil Abstr Ser 15:1

    Google Scholar 

  4. Chappell PE, Schneider JS, Kim P, Xu M, Lydon JP, O’Malley BW, Levine JE (1999) Absence of gonadotropin surges and gonadotropin-releasing hormone self-priming in ovariectomized (OVX), estrogen (E2)-treated, progesterone receptor knockout (PRKO) mice. Endocrinology 140:3653–3658

    Article  PubMed  CAS  Google Scholar 

  5. Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156–159

    Article  PubMed  CAS  Google Scholar 

  6. Denner LA, Weigel NL, Maxwell BL, Schrader WT, O’Malley BW (1990) Regulation of progesterone receptor-mediated transcription by phosphorylation. Science 250:1740–1743

    Article  PubMed  CAS  Google Scholar 

  7. Ferraretti AP, Garcia JE, Acosta AA, Jones GS (1983) Serum luteinizing hormone during ovulation induction with human menopausal gonadotropin for in vitro fertilization in normally menstruating women. Fertil Steril 40:742–747

    PubMed  CAS  Google Scholar 

  8. Fowler PA, Templeton A (1996) The nature and function of putative gonadotropin surge-attenuating/inhibiting factor (GnSAF/IF). Endocr Rev 17:103–120

    PubMed  CAS  Google Scholar 

  9. Fowler PA, Messinis IE, Cunningham P, Fraser M, Templeton AA (1993) Effects of gonadotrophin surge-attenuating factor on the two pools of gonadotrophin-releasing hormone-induced luteinizing hormone secretion in vitro. Hum Reprod 8:822–828

    PubMed  CAS  Google Scholar 

  10. Fowler PA, Bramley TA, MacGregor F, Templeton A (1995) Does GnSAF act through the pituitary protein kinase C pathway? J Reprod Fertil Abstr Ser 15:1

    Google Scholar 

  11. Fowler PA, Fraxer M, Cunningham C, Templeton A (1995) GnSAF suppresses both the synthesis and release of LH induced by GnRH. J Reprod Fertil Abstr Ser 15:1

    Google Scholar 

  12. Garrido-Gracia JC, Gordon A, Bellido C, Aguilar R, Barranco I, Millan Y, de Las Mulas JM, Sanchez-Criado JE (2007) The integrated action of oestrogen receptor isoforms and sites with progesterone receptor in the gonadotrope modulates LH secretion: evidence from tamoxifen-treated ovariectomized rats. J Endocrinol 193:107–119

    Article  PubMed  CAS  Google Scholar 

  13. Geiger JM, Plas-Roser S, Aron C (1980) Mechanisms of ovulation in female rats treated with FSH at the beginning of the estrous cycle: changes in pituitary responsiveness to luteinizing hormone releasing hormone (LHRH). Biol Reprod 22:837–845

    Article  PubMed  CAS  Google Scholar 

  14. Gordon A, Garrido-Gracia JC, Aguilar R, Sanchez-Criado JE (2009) Ovarian stimulation with FSH in the rat reduces proestrous GnRH-dependent LH secretion through a dual mechanism: inhibition of LH synthesis and release. Neurosci Lett 460:219–222

    Article  PubMed  CAS  Google Scholar 

  15. Gordon A, Garrido-Gracia JC, Aguilar R, Guil-Luna S, Millan Y, de Las Mulas JM, Sanchez-Criado JE (2009) Ovarian stimulation with FSH reduces phosphorylation of gonadotrope progesterone receptor and LH secretion in the rat. Reproduction 137:151–159

    Article  PubMed  CAS  Google Scholar 

  16. Gordon A, Garrido-Gracia JC, Aguilar R, Bellido C, Velasco JA, Millan Y, Tena-Sempere M, de Las M, Mulas J, Sanchez-Criado JE (2008) The ovary-mediated FSH attenuation of the LH surge in the rat involves a decreased gonadotroph progesterone receptor (PR) action but not PR expression. J Endocrinol 196:583–592

    Article  PubMed  CAS  Google Scholar 

  17. Gordon A, Aguilar R, Garrido-Gracia JC, Guil-Luna S, Sanchez Cespedes R, Millan Y, Watanabe G, Taya K, de Las M, Mulas J, Sanchez-Criado JE (2010) Immunoneutralization of inhibin in cycling rats increases follicle-stimulating hormone secretion, stimulates the ovary and attenuates progesterone receptor-dependent preovulatory luteinizing hormone secretion. Neuroendocrinology 91:291–301

    Article  PubMed  CAS  Google Scholar 

  18. Greenwood FC, Hunter WM, Glover JS (1963) The Preparation of I-131-Labelled Human Growth Hormone of High Specific Radioactivity. Biochem J 89:114–123

    PubMed  CAS  Google Scholar 

  19. Higuchi R, Fockler C, Dollinger G, Watson R (1993) Kinetic PCR analysis: real-time monitoring of DNA amplification reactions. Biotechnol NY 11:1026–1030

    Article  CAS  Google Scholar 

  20. Karligiotou E, Kollia P, Kallitsaris A, Messinis IE (2006) Expression of human serum albumin (HSA) mRNA in human granulosa cells: potential correlation of the 95 amino acid long carboxyl terminal of HSA to gonadotrophin surge-attenuating factor. Hum Reprod 21:645–650

    Article  PubMed  CAS  Google Scholar 

  21. Kitahara S, Winters SJ, Attardi B, Oshima H, Troen P (1990) Effects of castration on luteinizing hormone and follicle-stimulating hormone secretion by pituitary cells from male rats. Endocrinology 126:2642–2649

    Article  PubMed  CAS  Google Scholar 

  22. Koppenaal DW, Tijssen AM, van Dieten JA, de Koning J (1991) The self-priming action of LHRH is under negative FSH control through a factor released by the ovary: observations in female rats in vivo. J Endocrinol 129:205–211

    Article  PubMed  CAS  Google Scholar 

  23. Levine JE (1997) New concepts of the neuroendocrine regulation of gonadotropin surges in rats. Biol Reprod 56:293–302

    Article  PubMed  CAS  Google Scholar 

  24. Levine JE, Chappell PE, Schneider JS, Sleiter NC, Szabo M (2001) Progesterone receptors as neuroendocrine integrators. Front Neuroendocrinol 22:69–106

    Article  PubMed  CAS  Google Scholar 

  25. Messinis IE (2006) Ovarian feedback, mechanism of action and possible clinical implications. Hum Reprod Update 12:557–571

    Article  PubMed  CAS  Google Scholar 

  26. Pappa A, Seferiadis K, Fotsis T, Shevchenko A, Marselos M, Tsolas O, Messinis IE (1999) Purification of a candidate gonadotrophin surge attenuating factor from human follicular fluid. Hum Reprod 14:1449–1456

    Article  PubMed  CAS  Google Scholar 

  27. Ramey JW, Highsmith RF, Wilfinger WW, Baldwin DM (1987) The effects of gonadotropin-releasing hormone and estradiol on luteinizing hormone biosynthesis in cultured rat anterior pituitary cells. Endocrinology 120:1503–1513

    Article  PubMed  CAS  Google Scholar 

  28. Sanchez-Criado JE, Bellido C, Galiot F, Lopez FJ, Gaytan F (1990) A possible dual mechanism of the anovulatory action of antiprogesterone RU486 in the rat. Biol Reprod 42:877–886

    Article  PubMed  CAS  Google Scholar 

  29. Sánchez-Criado JE, Gordon A, Aguilar R, Garrido-Gracia JC, García Velasco JA, Guil-LUna S, Millan Y, Martín de las Mulas J (2009) Ovarian gonadotrope surge attenuating factor (GnSAF) from superovulated women inhibits GnRH self-priming in an estrous cycle stage dependent manner in the rat: involvement of gonadotrope progesterone receptor (PR) expression and action. Biol Reprod 81:1

    Article  Google Scholar 

  30. Schenken RS, Anderson WH, Hodgen GD (1984) Follicle-stimulating hormone increases ovarian vein nonsteroidal factors with gonadotropin-inhibiting activity. Fertil Steril 42:785–790

    PubMed  CAS  Google Scholar 

  31. Schuiling GA, Valkhof N, Koiter TR (1999) FSH inhibits the augmentation by oestradiol of the pituitary responsiveness to GnRH in the female rat. Hum Reprod 14:21–26

    Article  PubMed  CAS  Google Scholar 

  32. Sleiter N, Pang Y, Park C, Horton TH, Dong J, Thomas P, Levine JE (2009) Progesterone receptor A (PRA) and PRB-independent effects of progesterone on gonadotropin-releasing hormone release. Endocrinology 150:3833–3844

    Article  PubMed  CAS  Google Scholar 

  33. Tavoulari S, Frillingos S, Karatza P, Messinis IE, Seferiadis K (2004) The recombinant subdomain IIIB of human serum albumin displays activity of gonadotrophin surge-attenuating factor. Hum Reprod 19:849–858

    Article  PubMed  CAS  Google Scholar 

  34. Tena-Sempere M, Navarro VM, Mayen A, Bellido C, Sanchez-Criado JE (2004) Regulation of estrogen receptor (ER) isoform messenger RNA expression by different ER ligands in female rat pituitary. Biol Reprod 70:671–678

    Article  PubMed  CAS  Google Scholar 

  35. Tijssen AM, Helder MN, Chu ZW, de Koning J (1997) Intracellular antagonistic interaction between GnRH and gonadotrophin surge-inhibiting/attenuating factor bioactivity downstream of second messengers involved in the self-priming process. J Reprod Fertil 111:235–242

    Article  PubMed  CAS  Google Scholar 

  36. Vu Hai MT, Milgrom E (1978) Characterization and assay of the progesterone receptor in rat uterine cytosol. J Endocrinol 76:21–31

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This study was subsidized by grants BFU2008-00480 from DGICYT and P07-CVI-2559 from Junta de Andalucía (Spain). The authors are grateful to the National Hormone and Pituitary program (Baltimore, MD, USA) for the LH RIA kit.

Author information

Authors and Affiliations

  1. Department of Cell Biology, Physiology and Immunology, University of Córdoba, Avda. Menéndez Pidal s/n., 14004, Córdoba, Spain

    Ana Gordon, José Carlos Garrido-Gracia, José E. Sánchez-Criado & Rafaela Aguilar

Authors
  1. Ana Gordon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. José Carlos Garrido-Gracia
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. José E. Sánchez-Criado
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rafaela Aguilar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to José Carlos Garrido-Gracia.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gordon, A., Garrido-Gracia, J.C., Sánchez-Criado, J.E. et al. Involvement of rat gonadotrope progesterone receptor in the ovary-mediated inhibitory action of FSH on LH synthesis. J Physiol Biochem 67, 145–151 (2011). https://doi.org/10.1007/s13105-010-0057-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13105-010-0057-z

Keywords

Search

Navigation