Animal Reproduction (AR)
https://www.animal-reproduction.org/article/doi/10.1590/1984-3143-AR2022-0027
Animal Reproduction (AR)
ORIGINAL ARTICLE

Regulation of progesterone during follicular development by FSH and LH in sheep

Ziqiang Ding; Hongwei Duan; Wenbo Ge; Jianshu Lv; Jianlin Zeng; Wenjuan Wang; Tian Niu; Junjie Hu; Yong Zhang; Xingxu Zhao

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Abstract

Progesterone (P4) can participate in the development of female mammalian antral follicles through nuclear receptor (PGR). In this experiment, the differences of P4 synthesis and PGR expression in different developmental stages of sheep antral follicles (large > 5mm, medium 2-5mm, small < 2mm) were detected by enzyme-linked immunosorbent assay, immunohistochemistry, qRT-PCR and Western blotting. Secondly, sheep follicular granulosa cells were cultured in vitro. The effects of different concentrations of FSH and LH on P4 synthesis and PGR expression were studied. The results showed that acute steroid regulatory protein (StAR), cholesterol side chain lyase (P450scc) and 3β Hydroxysteroid dehydrogenase (3β-HSD) and PGR were expressed in antral follicles, and with the development of antral follicles in sheep, StAR, P450scc and the expression of 3β-HSD and PGR increased significantly. In vitro experiments showed that FSH and LH alone or together treatment could regulate P4 secretion and PGR expression in sheep follicular granulosa cells to varying degrees, hint P4 and PGR by FSH and LH, and LH was the main factor. Our results supplement the effects of FSH and LH on the regulation of P4 synthesis during follicular development, which provides new data for further study of steroid synthesis and function in follicular development.

Keywords

follicle-stimulating hormone, granulosa cells, luteinizing hormone, progesterone, sheep

References

Akison LK, Robker RL. The critical roles of progesterone receptor (PGR) in ovulation, oocyte developmental competence and oviductal transport in mammalian reproduction. Reprod Domest Anim. 2012;47(Suppl. 4):288-96. http://dx.doi.org/10.1111/j.1439-0531.2012.02088.x. PMid:22827383.

Barnett KR, Schilling C, Greenfeld CR, Tomic D, Flaws JA. Ovarian follicle development and transgenic mouse models. Hum Reprod Update. 2006;12(5):537-55. http://dx.doi.org/10.1093/humupd/dml022. PMid:16728463.

Bartlewski PM, Sohal J, Paravinja V, Baby T, Oliveira MEF, Murawski M, Schwarz T, Zieba DA, Keisler DH. Is progesterone the key regulatory factor behind ovulation rate in sheep? Domest Anim Endocrinol. 2017;58:30-8. http://dx.doi.org/10.1016/j.domaniend.2016.06.006. PMid:27639459.

Bishop CV, Hennebold JD, Kahl CA, Stouffer RL. Knockdown of progesterone receptor (PGR) in macaque granulosa cells disrupts ovulation and progesterone production. Biol Reprod. 2016;94(5):109. http://dx.doi.org/10.1095/biolreprod.115.134981. PMid:26985003.

Blaschka C, Sánchez-Guijo A, Zimmer B, Stöhr J, Kotarski F, Grothmann H, Hartmann MF, Wudy SA, Wrenzycki C. Temporal expression pattern of steroid-metabolizing enzymes in bovine COC during in vitro maturation employing different gonadotropin concentrations. Theriogenology. 2019;131:182-92. http://dx.doi.org/10.1016/j.theriogenology.2019.03.028. PMid:30981973.

Chaffin CL, Dissen GA, Stouffer RL. Hormonal regulation of steroidogenic enzyme expression in granulosa cells during the peri-ovulatory interval in monkeys. Mol Hum Reprod. 2000;6(1):11-8. http://dx.doi.org/10.1093/molehr/6.1.11. PMid:10611255.

Chen X, Fu J, Wang A. Expression of genes involved in progesterone receptor paracrine signaling and their effect on litter size in pigs. J Anim Sci Biotechnol. 2016;7(1):31. http://dx.doi.org/10.1186/s40104-016-0090-z. PMid:27231548.

D’Haeseleer M, Simoens P, Van den Broeck W. Cell-specific localization of progesterone receptors in the bovine ovary at different stages of the oestrous cycle. Anim Reprod Sci. 2007;98(3-4):271-81. http://dx.doi.org/10.1016/j.anireprosci.2006.03.013. PMid:16650698.

Drummond AE. The role of steroids in follicular growth. Reprod Biol Endocrinol. 2006;4(1):16. http://dx.doi.org/10.1186/1477-7827-4-16. PMid:16603089.

Duan H, Xiao L, Ge W, Yang S, Jiang Y, Lv J, Hu J, Zhang Y, Zhao X, Hua Y. Follicle-stimulating hormone and luteinizing hormone regulate the synthesis mechanism of dihydrotestosterone in sheep granulosa cells. Reprod Domest Anim. 2021;56(2):292-300. http://dx.doi.org/10.1111/rda.13837. PMid:33001490.

Duffy DM. Novel contraceptive targets to inhibit ovulation: the prostaglandin E2 pathway. Hum Reprod Update. 2015;21(5):652-70. http://dx.doi.org/10.1093/humupd/dmv026. PMid:26025453.

Durlej M, Tabarowski Z, Slomczynska M. Immunohistochemical study on differential distribution of progesterone receptor A and progesterone receptor B within the porcine ovary. Anim Reprod Sci. 2010;121(1-2):167-73. http://dx.doi.org/10.1016/j.anireprosci.2010.04.012. PMid:20478671.

Erickson GF, Garzo VG, Magoffin DA. Progesterone production by human granulosa cells cultured in serum free medium: effects of gonadotrophins and insulin-like growth factor I (IGF-I). Hum Reprod. 1991;6(8):1074-81. http://dx.doi.org/10.1093/oxfordjournals.humrep.a137487. PMid:1806564.

Garverick HA, Baxter G, Gong J, Armstrong DG, Campbell BK, Gutierrez CG, Webb R. Regulation of expression of ovarian mRNA encoding steroidogenic enzymes and gonadotrophin receptors by FSH and GH in hypogonadotrophic cattle. Reproduction. 2002;123(5):651-61. http://dx.doi.org/10.1530/rep.0.1230651. PMid:12006093.

Gong JG, Campbell BK, Bramley TA, Gutierrez CG, Peters AR, Webb R. Suppression in the secretion of follicle-stimulating hormone and luteinizing hormone, and ovarian follicle development in heifers continuously infused with a gonadotropin-releasing hormone agonist. Biol Reprod. 1996;55(1):68-74. http://dx.doi.org/10.1095/biolreprod55.1.68. PMid:8793060.

Herbison AE. Control of puberty onset and fertility by gonadotropin-releasing hormone neurons. Nat Rev Endocrinol. 2016;12(8):452-66. http://dx.doi.org/10.1038/nrendo.2016.70. PMid:27199290.

Holesh JE, Bass AN, Lord M. Physiology, ovulation. Treasure Island: StatPearls Publishing; 2021.

Hughes CHK, Murphy BD. Nuclear receptors: key regulators of somatic cell functions in the ovulatory process. Mol Aspects Med. 2021;78:100937. http://dx.doi.org/10.1016/j.mam.2020.100937. PMid:33288229.

Iwamasa J, Shibata S, Tanaka N, Matsuura K, Okamura H. The relationship between ovarian progesterone and proteolytic enzyme activity during ovulation in the gonadotropin-treated immature rat. Biol Reprod. 1992;46(2):309-13. http://dx.doi.org/10.1095/biolreprod46.2.309. PMid:1536908.

Ji XL, Liu X, Wang Z, Fang YC. Expression of ARID1A in polycystic ovary syndrome and its effect on the proliferation and apoptosis of ovarian granulosa cells. Ann Endocrinol (Paris). 2020;81(6):521-9. http://dx.doi.org/10.1016/j.ando.2020.11.008. PMid:33290750.

Kawashima I, Okazaki T, Noma N, Nishibori M, Yamashita Y, Shimada M. Sequential exposure of porcine cumulus cells to FSH and/or LH is critical for appropriate expression of steroidogenic and ovulation-related genes that impact oocyte maturation in vivo and in vitro. Reproduction. 2008;136(1):9-21. http://dx.doi.org/10.1530/REP-08-0074. PMid:18456902.

Kundu S, Pramanick K, Paul S, Bandyopadhyay A, Mukherjee D. Expression of LH receptor in nonpregnant mouse endometrium: LH induction of 3β-HSD and de novo synthesis of progesterone. J Endocrinol. 2012;215(1):151-65. http://dx.doi.org/10.1530/JOE-11-0486. PMid:22875961.

Lin P, Rui R. Effects of follicular size and FSH on granulosa cell apoptosis and atresia in porcine antral follicles. Mol Reprod Dev. 2010;77(8):670-8. http://dx.doi.org/10.1002/mrd.21202. PMid:20652999.

Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)). Method. Methods. 2001;25(4):402-8. http://dx.doi.org/10.1006/meth.2001.1262. PMid:11846609.

Lydon JP, DeMayo FJ, Funk CR, Mani SK, Hughes AR, Montgomery CA Jr, Shyamala G, Conneely OM, O’Malley BW. Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities. Genes Dev. 1995;9(18):2266-78. http://dx.doi.org/10.1101/gad.9.18.2266. PMid:7557380.

Mihm M, Baker PJ, Ireland JL, Smith GW, Coussens PM, Evans AC, Ireland JJ. Molecular evidence that growth of dominant follicles involves a reduction in follicle-stimulating hormone dependence and an increase in luteinizing hormone dependence in cattle. Biol Reprod. 2006;74(6):1051-9. http://dx.doi.org/10.1095/biolreprod.105.045799. PMid:16481595.

Mishra B, Park JY, Wilson K, Jo M. X-linked lymphocyte regulated gene 5c-like (Xlr5c-like) is a novel target of progesterone action in granulosa cells of periovulatory rat ovaries. Mol Cell Endocrinol. 2015;412:226-38. http://dx.doi.org/10.1016/j.mce.2015.05.008. PMid:26004213.

Nakano Y, Hasegawa T, Kashino C, Iwata N, Yamamoto K, Suyama A, Soejima Y, Nada T, Otsuka F. Aldosterone enhances progesterone biosynthesis regulated by bone morphogenetic protein in rat granulosa cells. J Steroid Biochem Mol Biol. 2020;203:105738. http://dx.doi.org/10.1016/j.jsbmb.2020.105738. PMid:32828828.

Natraj U, Richards JS. Hormonal regulation, localization, and functional activity of the progesterone receptor in granulosa cells of rat preovulatory follicles. Endocrinology. 1993;133(2):761-9. http://dx.doi.org/10.1210/endo.133.2.8344215. PMid:8344215.

Park-Sarge OK, Mayo KE. Regulation of the progesterone receptor gene by gonadotropins and cyclic adenosine 3′,5′-monophosphate in rat granulosa cells. Endocrinology. 1994;134(2):709-18. http://dx.doi.org/10.1210/endo.134.2.8299566. PMid:8299566.

Peiró R, Merchán M, Santacreu MA, Argente MJ, García ML, Folch JM, Blasco A. Identification of single-nucleotide polymorphism in the progesterone receptor gene and its association with reproductive traits in rabbits. Genetics. 2008;180(3):1699-705. http://dx.doi.org/10.1534/genetics.108.090779. PMid:18791246.

Pizzo F, Caloni F, Schreiber NB, Schutz LF, Totty ML, Albonico M, Spicer LJ. Direct effects of the algal toxin, domoic acid, on ovarian function: bovine granulosa and theca cells as an in vitro model. Ecotoxicol Environ Saf. 2015;113:314-20. http://dx.doi.org/10.1016/j.ecoenv.2014.12.009. PMid:25528487.

Sekar N, Garmey JC, Veldhuis JD. Mechanisms underlying the steroidogenic synergy of insulin and luteinizing hormone in porcine granulosa cells: joint amplification of pivotal sterol-regulatory genes encoding the low-density lipoprotein (LDL) receptor, steroidogenic acute regulatory (StAR) protein and cytochrome P450 side-chain cleavage (P450scc) enzyme. Mol Cell Endocrinol. 2000a;159(1-2):25-35. http://dx.doi.org/10.1016/S0303-7207(99)00203-8. PMid:10687849.

Sekar N, Lavoie HA, Veldhuis JD. Concerted regulation of steroidogenic acute regulatory gene expression by luteinizing hormone and insulin (or insulin-like growth factor I) in primary cultures of porcine granulosa-luteal cells. Endocrinology. 2000b;141(11):3983-92. http://dx.doi.org/10.1210/endo.141.11.7763. PMid:11089528.

Shih MC, Chiu YN, Hu MC, Guo IC, Chung BC. Regulation of steroid production: analysis of Cyp11a1 promoter. Mol Cell Endocrinol. 2011;336(1-2):80-4. http://dx.doi.org/10.1016/j.mce.2010.12.017. PMid:21195129.

Sirois J, Fortune JE. Lengthening the bovine estrous cycle with low levels of exogenous progesterone: a model for studying ovarian follicular dominance. Endocrinology. 1990;127(2):916-25. http://dx.doi.org/10.1210/endo-127-2-916. PMid:2373061.

Soumano K, Price CA. Ovarian follicular steroidogenic acute regulatory protein, low-density lipoprotein receptor, and cytochrome P450 side-chain cleavage messenger ribonucleic acids in cattle undergoing superovulation. Biol Reprod. 1997;56(2):516-22. http://dx.doi.org/10.1095/biolreprod56.2.516. PMid:9116155.

Sousa Abreu R, Penalva LO, Marcotte EM, Vogel C. Global signatures of protein and mRNA expression levels. Mol Biosyst. 2009;5(12):1512-26. http://dx.doi.org/10.1039/b908315d. PMid:20023718.

Sriraman V, Sinha M, Richards JS. Progesterone receptor-induced gene expression in primary mouse granulosa cell cultures. Biol Reprod. 2010;82(2):402-12. http://dx.doi.org/10.1095/biolreprod.109.077610. PMid:19726735.

Stock AE, Fortune JE. Ovarian follicular dominance in cattle: relationship between prolonged growth of the ovulatory follicle and endocrine parameters. Endocrinology. 1993;132(3):1108-14. http://dx.doi.org/10.1210/endo.132.3.8440173. PMid:8440173.

Sueldo C, Liu X, Peluso JJ. Progestin and AdipoQ receptor 7, progesterone membrane receptor component 1 (PGRMC1), and PGRMC2 and their role in regulating progesterone’s ability to suppress human granulosa/luteal cells from entering into the cell cycle. Biol Reprod. 2015;93(3):63. http://dx.doi.org/10.1095/biolreprod.115.131508. PMid:26203174.

Valderrama X, Ulloa-Leal C, Silva ME, Goicochea J, Apichela S, Argañaraz M, Sari L, Paiva L, Ratto VF, Ratto MH. β-NGF stimulates steroidogenic enzyme and VEGFA gene expression, and progesterone secretion via ERK 1/2 pathway in primary culture of llama granulosa cells. Front Vet Sci. 2020;7:586265. http://dx.doi.org/10.3389/fvets.2020.586265. PMid:33195615.

Wang S, Liu B, Liu W, Xiao Y, Zhang H, Yang L. The effects of melatonin on bovine uniparental embryos development in vitroand the hormone secretion of COCs. PeerJ. 2017;5:e3485. http://dx.doi.org/10.7717/peerj.3485. PMid:28698819.

Xiao L, Hu J, Zhao X, Song L, Zhang Y, Dong W, Zhang Q, Ma Y, Li F. Expression of melatonin and its related synthase and membrane receptors in the oestrous corpus luteum and corpus luteum verum of sheep. Reprod Domest Anim. 2018;53(5):1142-8. http://dx.doi.org/10.1111/rda.13218. PMid:29943511.

Yang JG, Yu CC, Li PS. Dexamethasone enhances follicle stimulating hormone-induced P450scc mRNA expression and progesterone production in pig granulosa cells. Chin J Physiol. 2001;44(3):111-9. PMid:11767283.

Zheng X, Price CA, Tremblay Y, Lussier JG, Carrière PD. Role of transforming growth factor-beta1 in gene expression and activity of estradiol and progesterone-generating enzymes in FSH-stimulated bovine granulosa cells. Reproduction. 2008;136(4):447-57. http://dx.doi.org/10.1530/REP-07-0316. PMid:18635743.
 


Submitted date:
02/19/2022

Accepted date:
06/14/2022

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