Concerted stimulation of rat granulosa cell deoxyribonucleic acid synthesis by sex steroids and follicle-stimulating hormone
Although follicle-stimulating hormone (FSH) and estrogens are known to be the main physiological stimuli for the development of the ovarian follicle in mammals, their growth-promoting activity has not been clearly established 'in vitro'. Furthermore, experimental evidence indicates that FS...
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1997
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09600760_v62_n1_p11_Bley http://hdl.handle.net/20.500.12110/paper_09600760_v62_n1_p11_Bley |
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paper:paper_09600760_v62_n1_p11_Bley2023-06-08T15:57:25Z Concerted stimulation of rat granulosa cell deoxyribonucleic acid synthesis by sex steroids and follicle-stimulating hormone Bley, Miguel Andrés Saragüeta, Patricia Barañao, José Lino S. 3beta androstanediol androstanolone androstenedione androsterone antiandrogen cyclic AMP derivative estradiol follitropin hydroxyflutamide insulin sex hormone somatomedin C animal cell article cell culture cell proliferation controlled study culture medium DNA synthesis dose response female granulosa cell in vitro study nonhuman rat signal transduction Although follicle-stimulating hormone (FSH) and estrogens are known to be the main physiological stimuli for the development of the ovarian follicle in mammals, their growth-promoting activity has not been clearly established 'in vitro'. Furthermore, experimental evidence indicates that FSH and estradiol can independently inhibit granulosa cell proliferation. The present study was aimed at examining the effect of sex steroids in combination with FSH, on DNA synthesis in rat granulosa cells cultured in completely defined medium. Estradiol and FSH, when added separately, produced a significant inhibition of [3H] thymidine incorporation. In contrast, a combination of a low dose of FSH (20 ng/ml) with estradiol (100 ng/ml) produced a shift in the period of maximal DNA synthesis from 96 to 48 h after plating. Dose response studies showed that estradiol effects were produced at physiological intraovarian concentrations (1-100 ng/ml), whereas the effects of FSH were biphasic, with high doses (200 ng/ml) being inhibitory. A similar biphasic dose response curve was observed with increasing concentrations of a cAMP derivative in the presence of maximally effective doses of either an aromatizable steroid (androstenedione), insulin or insulin-like growth factor I. Non-arematizable androgens (5α-dihydrotestosterone, 5α-androstane 3α-17β diol and androsterone) showed a potency comparable to that of estradiol. The effect of 5α-dihydrotestosterone was completely blocked by a specific antiandrogen (hydroxy-flutamide), indicating that it was mediated by the androgen receptor. The effects of estradiol and androgens were not additive. The interaction between estradiol and FSH was further amplified in the presence of a maximally effective dose of insulin. Data presented herein indicate that both estrogens and androgens are able to elicit a mitogenic response in purified granulosa cells, cultured in a completely defined medium, provided the cells are stimulated by a physiological dose of FSH. These results suggest that, during follicular development, the stimulus for granulosa cell proliferation is given by the concerted action of steroid and peptide hormones acting through different signalling pathways. Fil:Bley, M.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Saragüeta, P.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Barañao, J.L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 1997 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09600760_v62_n1_p11_Bley http://hdl.handle.net/20.500.12110/paper_09600760_v62_n1_p11_Bley |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
3beta androstanediol androstanolone androstenedione androsterone antiandrogen cyclic AMP derivative estradiol follitropin hydroxyflutamide insulin sex hormone somatomedin C animal cell article cell culture cell proliferation controlled study culture medium DNA synthesis dose response female granulosa cell in vitro study nonhuman rat signal transduction |
| spellingShingle |
3beta androstanediol androstanolone androstenedione androsterone antiandrogen cyclic AMP derivative estradiol follitropin hydroxyflutamide insulin sex hormone somatomedin C animal cell article cell culture cell proliferation controlled study culture medium DNA synthesis dose response female granulosa cell in vitro study nonhuman rat signal transduction Bley, Miguel Andrés Saragüeta, Patricia Barañao, José Lino S. Concerted stimulation of rat granulosa cell deoxyribonucleic acid synthesis by sex steroids and follicle-stimulating hormone |
| topic_facet |
3beta androstanediol androstanolone androstenedione androsterone antiandrogen cyclic AMP derivative estradiol follitropin hydroxyflutamide insulin sex hormone somatomedin C animal cell article cell culture cell proliferation controlled study culture medium DNA synthesis dose response female granulosa cell in vitro study nonhuman rat signal transduction |
| description |
Although follicle-stimulating hormone (FSH) and estrogens are known to be the main physiological stimuli for the development of the ovarian follicle in mammals, their growth-promoting activity has not been clearly established 'in vitro'. Furthermore, experimental evidence indicates that FSH and estradiol can independently inhibit granulosa cell proliferation. The present study was aimed at examining the effect of sex steroids in combination with FSH, on DNA synthesis in rat granulosa cells cultured in completely defined medium. Estradiol and FSH, when added separately, produced a significant inhibition of [3H] thymidine incorporation. In contrast, a combination of a low dose of FSH (20 ng/ml) with estradiol (100 ng/ml) produced a shift in the period of maximal DNA synthesis from 96 to 48 h after plating. Dose response studies showed that estradiol effects were produced at physiological intraovarian concentrations (1-100 ng/ml), whereas the effects of FSH were biphasic, with high doses (200 ng/ml) being inhibitory. A similar biphasic dose response curve was observed with increasing concentrations of a cAMP derivative in the presence of maximally effective doses of either an aromatizable steroid (androstenedione), insulin or insulin-like growth factor I. Non-arematizable androgens (5α-dihydrotestosterone, 5α-androstane 3α-17β diol and androsterone) showed a potency comparable to that of estradiol. The effect of 5α-dihydrotestosterone was completely blocked by a specific antiandrogen (hydroxy-flutamide), indicating that it was mediated by the androgen receptor. The effects of estradiol and androgens were not additive. The interaction between estradiol and FSH was further amplified in the presence of a maximally effective dose of insulin. Data presented herein indicate that both estrogens and androgens are able to elicit a mitogenic response in purified granulosa cells, cultured in a completely defined medium, provided the cells are stimulated by a physiological dose of FSH. These results suggest that, during follicular development, the stimulus for granulosa cell proliferation is given by the concerted action of steroid and peptide hormones acting through different signalling pathways. |
| author |
Bley, Miguel Andrés Saragüeta, Patricia Barañao, José Lino S. |
| author_facet |
Bley, Miguel Andrés Saragüeta, Patricia Barañao, José Lino S. |
| author_sort |
Bley, Miguel Andrés |
| title |
Concerted stimulation of rat granulosa cell deoxyribonucleic acid synthesis by sex steroids and follicle-stimulating hormone |
| title_short |
Concerted stimulation of rat granulosa cell deoxyribonucleic acid synthesis by sex steroids and follicle-stimulating hormone |
| title_full |
Concerted stimulation of rat granulosa cell deoxyribonucleic acid synthesis by sex steroids and follicle-stimulating hormone |
| title_fullStr |
Concerted stimulation of rat granulosa cell deoxyribonucleic acid synthesis by sex steroids and follicle-stimulating hormone |
| title_full_unstemmed |
Concerted stimulation of rat granulosa cell deoxyribonucleic acid synthesis by sex steroids and follicle-stimulating hormone |
| title_sort |
concerted stimulation of rat granulosa cell deoxyribonucleic acid synthesis by sex steroids and follicle-stimulating hormone |
| publishDate |
1997 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09600760_v62_n1_p11_Bley http://hdl.handle.net/20.500.12110/paper_09600760_v62_n1_p11_Bley |
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| _version_ |
1768543143321403392 |