Involvement of distinct signaling pathways in activin-induced increases in FSH secretion and enlargement of FSH cell population in the rat pituitary.

Activin-A induces increases in FSH secretion, as well as the number of immunoreactive FSH cells, in cultured rat pituitary cells. In this study, we examined whether mechanisms involved in these two actions of activin-A are identical or not, with respect to the involvement of cellular proliferation and of Ca2+-dependent signaling pathways. Treatment with activin-A (25 ng/ml) for 48 h caused increases in the number of cultured rat anterior pituitary cells that incorporated BrdU, a thymidine analog. The stimulatory effects of activin-A on FSH secretion and on the percentage of immunoreactive FSH cells were, however, not inhibited by the presence of the mitotic inhibitor cytosine arabinoside. On the other hand, the stimulatory effect of activin-A on the percentage of immunoreactive FSH cells was completely blocked in the presence of the Ca2+/calmodulin kinase inhibitor KN-62 or the L-type Ca2+ channel blocker nicardipine. Neither of these inhibitors, however, revealed significant influence on the effect of activin-A on FSH secretion. These results suggest that activin-A exhibits its dual effect on FSH cells without causing cellular proliferation. Furthermore, activin-A appears to induce increases in FSH secretion and enlargement of FSH cell population through distinct intracellular signaling pathways, the former through Ca2+-independent and the latter through Ca2+-dependent mechanisms.

[1]  Y. Hayashi,et al.  The role of activin type I receptors in activin A-induced growth arrest and apoptosis in mouse B-cell hybridoma cells. , 1998, Cellular signalling.

[2]  K. Yamato,et al.  Smad7 Is an Activin-inducible Inhibitor of Activin-induced Growth Arrest and Apoptosis in Mouse B Cells* , 1998, The Journal of Biological Chemistry.

[3]  M. Wilson,et al.  Activin subunit, follistatin, and activin receptor gene expression in the prepubertal female rat pituitary. , 1998, Biology of reproduction.

[4]  M. Kanzaki,et al.  Norepinephrine reverses the effects of activin A on DNA synthesis and apoptosis in cultured rat hepatocytes , 1996, Hepatology.

[5]  A. Bradley,et al.  Different phenotypes for mice deficient in either activins or activin receptor type II , 1995, Nature.

[6]  R. Schwall,et al.  Induction of apoptosis in the murine liver with recombinant human activin a , 1994, Hepatology.

[7]  K. Tasaka,et al.  Characterization of activin A-, activin AB- and activin B-responding cells by their responses to hypothalamic releasing hormones. , 1994, Biochemical and biophysical research communications.

[8]  H. Mogami,et al.  Modulation of growth of vascular smooth muscle cells by activin A. , 1993, Experimental cell research.

[9]  K. Inoue,et al.  Establishment of a folliculo-stellate-like cell line from a murine thyrotropic pituitary tumor. , 1992, Endocrinology.

[10]  K. Tasaka,et al.  Activin A increases cytosolic free calcium concentration in rat pituitary somatotropes. , 1992, Biochemical and biophysical research communications.

[11]  K. Shiota,et al.  Paracrine effect of folliculo-stellate cells on the growth factor-like action of activin A in anterior pituitary cultures. , 1992, Endocrinologia japonica.

[12]  Y. Eto,et al.  Evidence for the participation of endogenous activin A/erythroid differentiation factor in the regulation of erythropoiesis. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[13]  E. Ogata,et al.  Effects of activin A and somatostatin on intact FSH secretion and intracellular Ca2+ concentration in human FSH-secreting pituitary adenoma cells. , 1992, Biochemical and biophysical research communications.

[14]  K. Shiota,et al.  Effects of activin A on anterior pituitary cells fractionated by centrifugal elutriation , 1991, Molecular and Cellular Endocrinology.

[15]  J. Ramsdell.  Transforming Growth Factor-a and -0 Are Potent and Effective Inhibitors of GH4 Pituitary Tumor Cell Proliferation* , 1991 .

[16]  K. Shiota,et al.  Activin A increases the number of follicle-stimulating hormone cells in anterior pituitary cultures , 1990, Molecular and Cellular Endocrinology.

[17]  N. Billestrup,et al.  Inhibition of somatotroph growth and growth hormone biosynthesis by activin in vitro. , 1990, Molecular endocrinology.

[18]  E. Ogata,et al.  Dual effect of activin A on cell growth in Balb/c 3T3 cells. , 1989, Biochemical and biophysical research communications.

[19]  G. Risbridger,et al.  Inhibin and activin regulate [3H]thymidine uptake by rat thymocytes and 3T3 cells in vitro , 1989, Molecular and Cellular Endocrinology.

[20]  A. Mason,et al.  Selective and indirect modulation of human multipotential and erythroid hematopoietic progenitor cell proliferation by recombinant human activin and inhibin. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[21]  H. Shibai,et al.  Erythroid differentiation factor is encoded by the same mRNA as that of the inhibin beta A chain. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[22]  H. Shibai,et al.  Purification and characterization of erythroid differentiation factor (EDF) isolated from human leukemia cell line THP-1. , 1987, Biochemical and biophysical research communications.

[23]  J. Vaughan,et al.  Importance of FSH-releasing protein and inhibin in erythrodifferentiation , 1987, Nature.

[24]  Joan Vaughan,et al.  Purification and characterization of an FSH releasing protein from porcine ovarian follicular fluid , 1986, Nature.

[25]  Naoto Ueno,et al.  Pituitary FSH is released by a heterodimer of the β-subunits from the two forms of inhibin , 1986, Nature.

[26]  A. Khar,et al.  Effect of Hypothalamic Extracts on the Incorporation of [3H]-Thymidine by Pituitary Cells in Culture , 1978, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[27]  F. Greenwood,et al.  THE PREPARATION OF I-131-LABELLED HUMAN GROWTH HORMONE OF HIGH SPECIFIC RADIOACTIVITY. , 1963, The Biochemical journal.

[28]  T. Nishihara,et al.  Induction of apoptosis in B lineage cells by activin A derived from macrophages. , 1995, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[29]  E. Ogata,et al.  Effects of activin A on ionic channels in human FSH‐secreting tumour cells. , 1994, The Journal of physiology.

[30]  W. Vale,et al.  Gonadal and extragonadal expression of inhibin alpha, beta A, and beta B subunits in various tissues predicts diverse functions. , 1988, Proceedings of the National Academy of Sciences of the United States of America.