TY - JOUR
T1 - The Effects of Insulin on 3β-Hydroxysteroid Dehydrogenase Expression in Human Luteinized Granulosa Cells
AU - McGee, Elizabeth
AU - Sawetawan, Chiravudh
AU - Bird, Ian
AU - Rainey, William E.
AU - Carr, Bruce R.
PY - 1995/5
Y1 - 1995/5
N2 - Objective: We determined the relative effects of insuling and FSH on progesterone accumulation as well as activity, protein content, and mRNA expression of 3β-hydroxysteroid dehydrogenase (3βHSD) in human luteinized granulosa cells. Methods: Luteinized granulosa cells obtained from women undergoing in vitro fertilization were plated and grown to near confluence and treatd with FSH, insulin, or a combination of insulin and FSH. Progesterone production as well as enzyme activity, protein content, and mRNA expression for 3βHSD were evaluated. Results: Progesterone production was not affected by insulin alone but increased threefold in the presence of FSH (50 ng/μL) alone. The presence of FSH plus insulin (100 nmol/L) caused a significant increase in progesterone accumulation greater than that of FSH alone. The already high basal levels of 3βHSD activity were unaffected by insulin alone but increased 1.7-fold in the presence of FSH. The combination of FSH (50 ng/mL) and insulin (100 nmol/L) increased activity 1.3-fold over FSH alone (P <.02) Insulin (greater than 100 nmol/L) alone increased 3βHSD protein content as measured by Western analysis 1.8-2fold over basal levels, whereas FSH alone increased protein contetn 2.8-fold, and was further augmented by the addition of insulin in a dose-related fashion up to 3.5-fold over basal levels. Insulin increased 3βHSD mRNA twofold over basal levels; FSH alone increased mRNA expression of 3βHSD 3.2-fold. In the presence of insulin plus FSH, 3βHSD mRNA expression increased 7.6-fold over basal levels. For comparison, insulin also stimulated cytochrome P450 aromatase activity, P450 aromatase protein, and mRNA but to a greater degree than that seen for 3βHSD. Conclusion: Insulin is a regular of both 3βHSD and aromatase expression in human granulosa cells. Elevated insulin levels could therefore affect steroid production in human granulosa cells and presumably alter the menstrual cycle and fertility.
AB - Objective: We determined the relative effects of insuling and FSH on progesterone accumulation as well as activity, protein content, and mRNA expression of 3β-hydroxysteroid dehydrogenase (3βHSD) in human luteinized granulosa cells. Methods: Luteinized granulosa cells obtained from women undergoing in vitro fertilization were plated and grown to near confluence and treatd with FSH, insulin, or a combination of insulin and FSH. Progesterone production as well as enzyme activity, protein content, and mRNA expression for 3βHSD were evaluated. Results: Progesterone production was not affected by insulin alone but increased threefold in the presence of FSH (50 ng/μL) alone. The presence of FSH plus insulin (100 nmol/L) caused a significant increase in progesterone accumulation greater than that of FSH alone. The already high basal levels of 3βHSD activity were unaffected by insulin alone but increased 1.7-fold in the presence of FSH. The combination of FSH (50 ng/mL) and insulin (100 nmol/L) increased activity 1.3-fold over FSH alone (P <.02) Insulin (greater than 100 nmol/L) alone increased 3βHSD protein content as measured by Western analysis 1.8-2fold over basal levels, whereas FSH alone increased protein contetn 2.8-fold, and was further augmented by the addition of insulin in a dose-related fashion up to 3.5-fold over basal levels. Insulin increased 3βHSD mRNA twofold over basal levels; FSH alone increased mRNA expression of 3βHSD 3.2-fold. In the presence of insulin plus FSH, 3βHSD mRNA expression increased 7.6-fold over basal levels. For comparison, insulin also stimulated cytochrome P450 aromatase activity, P450 aromatase protein, and mRNA but to a greater degree than that seen for 3βHSD. Conclusion: Insulin is a regular of both 3βHSD and aromatase expression in human granulosa cells. Elevated insulin levels could therefore affect steroid production in human granulosa cells and presumably alter the menstrual cycle and fertility.
KW - 3β-hydroxysteroid dehydrogenase
KW - FSH
KW - aromatase
KW - granulosa cells
KW - insulin
KW - luteinization
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U2 - 10.1177/107155769500200306
DO - 10.1177/107155769500200306
M3 - Article
C2 - 9420856
AN - SCOPUS:0028988691
SN - 1071-5576
VL - 2
SP - 535
EP - 541
JO - Journal of the Society for Gynecologic Investigation
JF - Journal of the Society for Gynecologic Investigation
IS - 3
ER -