INVESTIGADORES
MERONI Silvina Beatriz
artículos
Título:
Signal transduction pathways in FSH regulation of rat Sertoli cell proliferation.
Autor/es:
RIERA MARÍA FERNANDA; REGUEIRA MARIANA; GALARDO MARÍA NOEL; PELLIZZARI ELIANA HERMINIA; MERONI SILVINA BEATRIZ; CIGORRAGA SELVA BEATRIZ
Revista:
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
Editorial:
AMER PHYSIOLOGICAL SOC
Referencias:
Año: 2012 vol. 302 p. 914 - 924
ISSN:
0193-1849
Resumen:
The final number of Sertoli cells
reached during the proliferative periods determines sperm production
capacity in adulthood. It is well known that FSH is the major Sertoli
cell mitogen; however, little is known about the signal transduction
pathways that regulate the proliferation of Sertoli cells. The hypothesis
of this investigation was that FSH regulates proliferation through
a PI3K/Akt/mTORC1 pathway, and additionally, AMPK-dependent
mechanisms counteract FSH proliferative effects. The present study
was performed in 8-day-old rat Sertoli cell cultures. The results
presented herein show that FSH, in addition to increasing p-Akt,
p-mTOR, and p-p70S6K levels, increases p-PRAS40 levels, probably
contributing to improving mTORC1 signaling. Furthermore, the decrease
in FSH-stimulated p-Akt, p-mTOR, p-p70S6K, and p-PRAS40
levels in the presence of wortmannin emphasizes the participation of
PI3K in FSH signaling. Additionally, the inhibition of FSH-stimulated
Sertoli cell proliferation by the effect of wortmannin and rapamycin
point to the relevance of the PI3K/Akt/mTORC1 signaling pathway in
the mitotic activity of FSH. On the other hand, by activating AMPK,
several interesting observations were made. Activation of AMPK
produced an increase in Raptor phosphorylation, a decrease in
p70S6K phosphorylation, and a decrease in FSH-stimulated Sertoli
cell proliferation. The decrease in FSH-stimulated cell proliferation
was accompanied by an increased expression of the CDKIs
p19INK4d, p21Cip1, and p27Kip1. In summary, it is concluded that
FSH regulates Sertoli cell proliferation with the participation of a
PI3K/Akt/mTORC1 pathway and that AMPK activation may be
involved in the detention of proliferation by, at least in part, a decrease
in mTORC1 signaling and an increase in CDKIs expression.