Estamos trabajando para incorporar este artículo al repositorio
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor


In the present study, we have examined the role of hormones and growth factors in regulating dimeric inhibin production in immature rat granulosa cells. Purified granulosa cells from estrogen-primed immature rats were cultured under defined conditions. Inhibins A and B in the culture media were measured using a two-site enzyme-linked immunosorbent assay specific for each dimer. Under basal conditions, granulosa cells produced 14-fold more inhibin A than inhibin B (inhibin A, 2.0; inhibin B, 0.14 ng/ml, measured against human standards; average A/B apparent ratio, 14). Addition of increasing doses of FSH elicited dose-dependent increases in both inhibins, the effects being more pronounced on inhibin A than on inhibin B (9.4- and 4.1-fold increases, respectively; average A/B ratio, 34). Estradiol, when added alone, stimulated inhibin A production 3- to 6-fold, whereas minor changes were observed in inhibin B production. Insulin-like growth factor-I produced a similar stimulation of both inhibins (3-fold stimulation over control). This growth factor, however, induced a marked dissociation in the sensitivity of inhibins A and B to FSH stimulation, with maximal stimulation of inhibin B observed at comparatively lower concentrations of the gonadotropin. Transforming growth factor-β (TGF-β, 5 ng/ml) had a more marked stimulatory effect on inhibin B than on inhibin A production (7- to 14-fold vs. 2- to 5-fold for inhibin B and A, respectively). A more pronounced differential stimulation of inhibin B was also exerted by another member of the TGF-β superfamily, activin A (A/B ratio, 0.66). This preferential stimulation of inhibin B by TGF-β and activin A was amplified in the presence of FSH. Coculture of rat granulosa cells with freshly isolated bovine oocytes was also associated with a marked stimulation of inhibin B production (100-fold increase) and a comparatively lower stimulation of inhibin A (10-fold increase; A/B ratio, 1). The discrepancy between the proportion of inhibin dimers in serum (A/B ratio, 0.13) and those produced by untreated granulosa cells may suggest that intraovarian factors, such as TGF-β, activin A, or oocyte-derived factor(s), are responsible for the shift of the ratio toward the predominance of inhibin B.


Documento: Artículo
Título:Dimeric inhibin A and B production are differentially regulated by hormones and local factors in rat granulosa cells
Autor:Lanuza, G.M.; Groome, N.P.; Barañao, J.L.; Campo, S.
Filiación:Instituto de Biología Experimental, CONICET, Universidad de Buenos Aires, 1428, Argentina
School of Biological and Molecular Sciences, Oxford Brookes University, Oxford OX3 OBP, United Kingdom
Centro de Investigaciones Endocrinológicas, Hospital de Niños Ricardo Gutierrez, Buenos Aires, 1425, Argentina
Vuelta de Obligado 2490, 1428 Buenos Aires, Argentina
Palabras clave:activin A; estradiol; follitropin; growth factor; hormone; inhibin A; inhibin B; transforming growth factor beta; animal cell; article; cattle; coculture; concentration response; controlled study; enzyme linked immunosorbent assay; granulosa cell; hormonal regulation; hormone action; hormone sensitivity; nonhuman; oocyte; priority journal; protein blood level; protein determination; protein synthesis; rat
Página de inicio:2549
Página de fin:2554
Título revista:Endocrinology
Título revista abreviado:Endocrinology
CAS:activin A, 104625-48-1; estradiol, 50-28-2; follitropin, 9002-68-0; inhibin B, 115088-91-0


  • Burger, H.G., Evidence for a negative feedback role of inhibin in follicle stimulating hormone regulation in women (1993) Hum Reprod, 8 (SUPPL. 2), pp. 129-132
  • Woodruff, T.K., Mather, J.P., Inhibin, activin and the female reproductive axis (1995) Annu Rev Physiol, 57, pp. 219-244
  • Findlay, J.K., An update on the roles of inhibin, activin, and follistatin as local regulators of folliculogenesis (1993) Biol Reprod, 48, pp. 15-23
  • Knight, P.G., Beard, A.J., Wrathall, J.H., Castillo, R.J., Evidence that the bovine ovary secretes large amounts of monomeric inhibin alpha subunit and its isolation from bovine follicular fluid (1989) J Mol Endocrinol, 2, pp. 189-200
  • Robertson, D., Burger, H.G., Sullivan, J., Cahir, N., Groome, N., Poncelet, E., Franchimont, P., Mather, J.P., Biological and immunological characterization of inhibin forms in human plasma (1996) J Clin Endocrinol Metab, 81, pp. 669-676
  • Robertson, D.M., Cahir, N., Findlay, J.K., Burger, H.G., Groome, N., The biological and immunological characterization of inhibin A and B forms in human follicular fluid and plasma (1997) J Clin Endocrinol Metab, 82, pp. 889-896
  • Bhasin, S., De Kretser, D.D.M., Drew, C.R., Measurement of circulating inhibin levels: Revisiting the inhibin hypothesis (1996) J Clin Endocrinol Metab, 81, pp. 1318-1320
  • McLachlan, R.I., Robertson, D.M., Burger, H.G., De Kretser, D.M., The radioimmunoassay of bovine and human follicular fluid and serum inhibin (1986) Mol Cell Endocrinol, 46, pp. 175-185
  • Schneyer, A.L., Mason, A.J., Burton, L.E., Ziegner, J.R., Crowley W.F., Jr., Immunoreactive inhibin α-subunit in human serum: Implications for radioimmunoassay (1990) J Clin Endocrinol Metab, 70, pp. 1208-1212
  • Groome, N., Ultrasensitive two-site assays for inhibin-A and activin-A using monoclonal antibodies raised to synthetic peptides (1991) J Immunol Methods, 145, pp. 65-69
  • Groome, N., O'Brien, M., Immunoassays for inhibin and its subunits. Further applications of the synthetic peptide approach (1993) J Immunol Methods, 165, pp. 167-176
  • Groome, N.P., Illingworth, P.J., O'Brien, M., Priddle, J., Weaver, K., McNeilly, A.S., Quantification of inhibin pro-αC-containing forms in human serum by a new ultrasensitive two-site enzyme-linked immunosorbent assay (1995) J Clin Endocrinol Metab, 80, pp. 2926-2932
  • Groome, N.P., Illingworth, P.J., O'Brien, M., Pai, R., Rodger, F.E., Mather, J.P., McNeilly, A.S., Measurement of dimeric inhibin B throughout the human menstrual cycle (1996) J Clin Endocrinol Metab, 81, pp. 1401-1405
  • Groome, N.P., Illingworth, P.J., O'Brien, M., Cooke, I., Ganesan, T.S., Baird, D.T., McNeilly, A.S., Detection of dimeric inhibin throughout the human menstrual cycle by two-site enzyme immunoassay (1994) Clin Endocrinol (Oxf), 40, pp. 717-723
  • Woodruff, T.K., Besecke, L.M., Groome, N., Draper, L.B., Schwartz, N.B., Weiss, J., Inhibin A and inhibin B are inversely correlated to follicle-stimulating hormone, yet are discordant during the follicular phase of the rat estrous cycle, and inhibin A is expressed in a sexually dimorphic manner (1996) Endocrinology, 137, pp. 5463-5467
  • Bley, M.A., Simón, J.C., Estévez, A.G., Jiménez de Asúa, L., Barañao, J.L., Effect of follicle-stimulating hormone on insulin-like growth factor-I-stimulated rat granulosa cell deoxyribonucleic acid synthesis (1992) Endocrinology, 131, pp. 1223-1229
  • Lanuza, G.M., Fischman, M.L., Barañao, J.L., Growth promoting activity of oocytes on granulosa cells is decreased upon meiotic maturation (1998) Dev Biol, 197, pp. 129-139
  • Sokal, R.R., Rohlf, F.J., (1995) Biometry, ed 3, , W. H. Freeman and Company, New York
  • DeLean, A., Munson, P.J., Rodbard, D., Simultaneous analysis of families of sigmoidal curves: Application to bioassay, radioligand assay and physiological dose-response curves (1978) Am J Physiol, 235, pp. E97-E102
  • Zhiwen, Z., Findlay, J.K., Carson, R.S., Herington, A.C., Burger, H.G., Transforming growth factor beta enhances basal and FSH-stimulated inhibin production by rat granulosa cells in vitro (1988) Mol Cell Endocrinol, 58, pp. 161-166
  • Xiao, S., Farnworth, P.G., Findlay, J.K., Interaction between activin and follicle-stimulating hormone-suppressing protein/follistatin in the regulation of basal inhibin production by cultured rat granulosa cells (1992) Endocrinology, 131, pp. 2365-2370
  • Meunier, H., Cajander, S.B., Roberts, V.J., Rivier, C., Sawchenko, P.E., Hsueh, A.J., Vale, W., Rapid changes in the expression of inhibin alpha-, beta A-, and beta B-subunits in ovarian cell types during the rat estrous cycle (1988) Mol Endocrinol, 2, pp. 1352-1363
  • Turner, I.M., Saunders, P.T.K., Shimasaki, S., Hillier, S.G., Saunders, P.T., Regulation of inhibin subunit gene expression by FSH and estradiol in cultured rat granulosa cells (1989) Endocrinology, 125, pp. 2790-2792
  • LaPolt, P.S., Piquette, G.N., Soto, D., Sincich, C., Hsueh, A.J., Regulation of inhibin subunit messenger ribonucleic acid levels by gonadotropins, growth factors, and gonadotropin-releasing hormone in cultured rat granulosa cells (1990) Endocrinology, 127, pp. 823-831
  • Erämaa, M., Tuuri, T., Hilden, K., Ritvos, O., Regulation of inhibin alpha- and beta A-subunit messenger ribonucleic acid levels by chorionic gonadotropin and recombinant follicle-stimulating hormone in cultured human granulosaluteal cells (1994) J Clin Endocrinol Metab, 79, pp. 1670-1677
  • Aloi, J.A., Dalkin, A.C., Schwartz, N.B., Yasin, M., Mann, B., Haisenleder, D.J., Marshall, J.C., Ovarian inhibin subunit gene expression: Regulation by gonadotropins and estradiol (1995) Endocrinology, 136, pp. 1227-1232
  • Erämaa, M., Ritvos, O., Transforming growth factor-β1 and -β2 induce inhibin and activin βB subunit messenger ribonucleic acid levels in cultured human granulosa-luteal cells (1996) Fertil Steril, 65, pp. 954-960
  • Bley, M.A., Saragüeta, P.E., Barañao, J.L., Concerted stimulation of rat granulosa cell deoxyribonucleic acid synthesis by sex steroids and follicle-stimulating hormone (1997) J Steroid Biochem Mol Biol, 62, pp. 11-19
  • Miró, F., Hillier, S.G., Modulation of granulosa cell deoxyribonucleic acid synthesis and differentiation by activin (1996) Endocrinology, 137, pp. 464-468
  • Michel, U., Krozowski, Z., McMaster, J., Jinghua, Y., Findlay, J.K., The biphasic modulation of inhibin mRNA levels and secretion by PMSG in rat granulosa cells in vitro (1991) Reprod Fertil Dev, 3, pp. 215-226
  • Arey, B.J., Stevis, P.E., Deecher, D.C., Shen, E.S., Frail, D.E., Negro-Vilar, A., Lopez, F.J., Induction of promiscuous G protein coupling of the follicle-stimulating hormone (FSH) receptor: A novel mechanism for transducing pleiotropic actions of FSH isoforms (1997) Mol Endocrinol, 11, pp. 517-526
  • Li, D., Kubo, T., Kim, H., Shimasaki, S., Erickson, G.F., Endogenous insulin-like growth factor-I is obligatory for stimulation of rat inhibin alpha-subunit expression by follicle-stimulating hormone (1998) Biol Reprod, 58, pp. 219-225
  • Kubo, T., Shimasaki, S., Kim, H., Li, D., Erickson, G.F., Activin-induced inhibin alpha-subunit production by rat granulosa cells requires endogenous insulin-like growth factor-I (1998) Biol Reprod, 58, pp. 712-718
  • Erämaa, M., Hilden, K., Tuuri, T., Ritvos, O., Regulation of inhibin/activin subunit messenger ribonucleic acids (mRNAs) by activin A and expression of activin receptor mRNAs in cultured human granulosa-luteal cells (1995) Endocrinology, 136, pp. 4382-4389
  • Tirone, E., D'Alessandris, C., Hascall, V.C., Siracusa, G., Salustri, A., Hyaluronan synthesis by mouse cumulus cells is regulated by interactions between follicle-stimulating hormone (or epidermal growth factor) and a soluble oocyte factor (or transforming growth factor beta1) (1997) J Biol Chem, 272, pp. 4787-4794
  • Vanderhyden, B.C., Species differences in the regulation of cumulus expansion by an oocyte-secreted factor(s) (1993) J Reprod Fertil, 98, pp. 219-227
  • Eppig, J.J., Wigglesworth, K., Pendola, F., Hirao, Y., Murine oocytes suppress expression of luteinizing hormone receptor messenger ribonucleic acid by granulosa cells (1997) Biol Reprod, 56, pp. 976-984
  • McGrath, S.A., Esquela, A.F., Lee, S.J., Oocyte-specific expression of growth/differentiation factor-9 (1995) Mol Endocrinol, 9, pp. 131-136
  • Dong, J., Albertini, D.F., Nishimori, K., Kumar, T.R., Lu, N., Matzuk, M.M., Growth differentiation factor-9 is required during early ovarian folliculogenesis (1996) Nature, 383, pp. 531-535
  • Pineau, C., Sharpe, R.M., Saunders, P.T., Gerard, N., Jegou, B., Regulation of Sertoli cell inhibin production and of inhibin alpha-subunit mRNA levels by specific germ cell types (1990) Mol Cell Endocrinol, 72, pp. 13-22
  • Foucault, P., Drosdowsky, M.A., Carreau, S., Germ cell and Sertoli cell interactions in human testis: Evidence for stimulatory and inhibitory effects (1994) Hum Reprod, 9, pp. 2062-2068
  • Mather, J.P., Moore, A., Li, R.H., Activins, inhibins, and follistatins: Further thoughts on a growing family of regulators (1997) Proc Soc Exp Biol Med, 215, pp. 209-222
  • Fahy, P.A., Wilson, C.A., Beard, A.J., Groome, N.P., Knight, P.G., Changes in inhibin-A (α-βA dimer) and total a inhibin in the peripheral circulation and ovaries of rats after gonadotrophin-induced follicular development and during the normal oestrous cycle (1995) J Endocrinol, 147, pp. 271-283
  • Smitz, J., Cortvrindt, R., Inhibin A and B secretion in mouse preantral follicle culture (1998) Hum Reprod, 13, pp. 927-935
  • Hillier, S.G., Miró, F., Mather, J.P., Thong, K.J., Comparison of the effects of the inhibin-A and inhibin-B on androgen production by human theca cells in vitro (1997) FSH Action and Intraovarian Regulation, 6, pp. 137-144. , Fauser BCJM (ed). The Parthenon Publishing Group, New York, London
  • Stock, A.E., Woodruff, T.K., Smith, L.C., Effects of inhibin A and activin A during in vitro maturation of bovine oocytes in hormone- and serum-free medium (1997) Biol Reprod, 56, pp. 1559-1564
  • Miller, K.F., Xie, S., Pope, W.F., Immunoreactive inhibin in follicular fluid is related to meiotic stage of the oocyte during final maturation of the porcine follicle (1991) Mol Reprod Dev, 28, pp. 35-39


---------- APA ----------
Lanuza, G.M., Groome, N.P., Barañao, J.L. & Campo, S. (1999) . Dimeric inhibin A and B production are differentially regulated by hormones and local factors in rat granulosa cells. Endocrinology, 140(6), 2549-2554.
---------- CHICAGO ----------
Lanuza, G.M., Groome, N.P., Barañao, J.L., Campo, S. "Dimeric inhibin A and B production are differentially regulated by hormones and local factors in rat granulosa cells" . Endocrinology 140, no. 6 (1999) : 2549-2554.
---------- MLA ----------
Lanuza, G.M., Groome, N.P., Barañao, J.L., Campo, S. "Dimeric inhibin A and B production are differentially regulated by hormones and local factors in rat granulosa cells" . Endocrinology, vol. 140, no. 6, 1999, pp. 2549-2554.
---------- VANCOUVER ----------
Lanuza, G.M., Groome, N.P., Barañao, J.L., Campo, S. Dimeric inhibin A and B production are differentially regulated by hormones and local factors in rat granulosa cells. Endocrinology. 1999;140(6):2549-2554.