TY - JOUR
T1 - Androgens regulate follicle stage-dependent pro-and anti-apoptosis in teleost ovaries through ZIP9 activation of different G proteins
AU - Converse, Aubrey
AU - Thomas, Peter
N1 - Publisher Copyright:
© 2019 Published by Oxford University Press on behalf of Society for the Study of Reproduction 2019.
PY - 2019/8/1
Y1 - 2019/8/1
N2 - Androgens mediate a number of processes in mammalian and teleost ovaries in a follicle-stage dependent manner, including follicle growth, survival, and apoptosis. We recently reported that the membrane androgen receptor ZIP9 mediates apoptosis in Atlantic croaker granulosa/theca (G/T) cells from mature ovarian follicles, but the effects of androgens on early stage G/T cells in this model remains unknown. Here we show that testosterone mediates pro-and anti-apoptotic responses in a follicle stage-dependent manner in croaker ovarian follicle cells. Testosterone treatment decreased the incidence of apoptosis in G/T cells from early stage follicles (diameter <300 μm) but increased apoptosis in G/T cells from late stage follicles (diameter >400 μm). Small interfering RNA targeting ZIP9, but not the nuclear androgen receptor, blocked the anti-apoptotic response, indicating ZIP9 mediates anti-apoptotic in addition to pro-apoptotic responses. Testosterone treatment of early stage G/T cells resulted in opposite signaling outcomes from those previously characterized for the ZIP9-mediated apoptotic response including decreased cAMP and intracellular free zinc levels, and downregulation of pro-apoptotic member mRNA expression. While ZIP9-mediated apoptosis involves activation of a stimulatory G protein (Gs), activators of Gs signaling antagonized the anti-apoptotic response. Proximity ligation and G protein activation assays indicated that in G/T cells from early stage follicles ZIP9 is in close proximity and activates an inhibitory G protein, while in G/T cells from late stage follicles ZIP9 is in close proximity and activates Gs. This study demonstrates that ZIP9 mediates opposite survival responses of croaker G/T cells by activating different G proteins in a follicle stage-dependent manner.
AB - Androgens mediate a number of processes in mammalian and teleost ovaries in a follicle-stage dependent manner, including follicle growth, survival, and apoptosis. We recently reported that the membrane androgen receptor ZIP9 mediates apoptosis in Atlantic croaker granulosa/theca (G/T) cells from mature ovarian follicles, but the effects of androgens on early stage G/T cells in this model remains unknown. Here we show that testosterone mediates pro-and anti-apoptotic responses in a follicle stage-dependent manner in croaker ovarian follicle cells. Testosterone treatment decreased the incidence of apoptosis in G/T cells from early stage follicles (diameter <300 μm) but increased apoptosis in G/T cells from late stage follicles (diameter >400 μm). Small interfering RNA targeting ZIP9, but not the nuclear androgen receptor, blocked the anti-apoptotic response, indicating ZIP9 mediates anti-apoptotic in addition to pro-apoptotic responses. Testosterone treatment of early stage G/T cells resulted in opposite signaling outcomes from those previously characterized for the ZIP9-mediated apoptotic response including decreased cAMP and intracellular free zinc levels, and downregulation of pro-apoptotic member mRNA expression. While ZIP9-mediated apoptosis involves activation of a stimulatory G protein (Gs), activators of Gs signaling antagonized the anti-apoptotic response. Proximity ligation and G protein activation assays indicated that in G/T cells from early stage follicles ZIP9 is in close proximity and activates an inhibitory G protein, while in G/T cells from late stage follicles ZIP9 is in close proximity and activates Gs. This study demonstrates that ZIP9 mediates opposite survival responses of croaker G/T cells by activating different G proteins in a follicle stage-dependent manner.
KW - androgens/androgen receptor
KW - apoptosis
KW - fish reproduction
KW - granulosa cells
KW - hormone action
KW - steroid hormone receptors
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U2 - 10.1093/biolre/ioz086
DO - 10.1093/biolre/ioz086
M3 - Article
C2 - 31074766
AN - SCOPUS:85072058017
SN - 0006-3363
VL - 101
SP - 377
EP - 391
JO - Biology of reproduction
JF - Biology of reproduction
IS - 2
ER -