Developmental response by Leydig cells to acidic and basic fibroblast growth factor

Area of Science:

• Reproductive biology
• Endocrinology
• Cell signaling

Background:

• Leydig cells are crucial for testosterone production.
• Fibroblast growth factors (FGFs) are signaling proteins with diverse biological roles.
• Heparan sulfate proteoglycans (HSPG) are involved in growth factor binding and signaling.

Purpose of the Study:

• To investigate the effects of acidic (FGF-1) and basic (FGF-2) fibroblast growth factors on Leydig cell steroidogenesis.
• To determine if these effects are developmentally regulated across different stages of Leydig cell maturation.
• To elucidate the role of heparan sulfate proteoglycans (HSPG) in mediating FGF actions.

Main Methods:

• Primary Leydig cell cultures from rats at 5, 21, and 90 days of age.
• Treatment with FGF-1, FGF-2, and luteinizing hormone (LH).
• Assessment of testosterone and 5 alpha-androstane-3 alpha, 17 beta-diol production.
• Inhibition studies using protamine sulfate and sodium chlorate to block HSPG activity.

Main Results:

• FGF-1 and FGF-2 stimulated basal testosterone production in fetal Leydig cells (day 5) and basal 5 alpha-androstane-3 alpha, 17 beta-diol in immature Leydig cells (day 21).
• These stimulatory effects were dependent on heparan sulfate proteoglycans (HSPG) and were blocked by protamine sulfate and sodium chlorate.
• FGF-1 and FGF-2 had no effect on basal testosterone production in adult Leydig cells (day 90); however, FGF-1 inhibited LH-stimulated testosterone production in a dose-dependent manner.
• Differential effects of FGF-1 and FGF-2 were observed on the same Leydig cell types, suggesting distinct roles.

Conclusions:

• The effects of FGF-1 and FGF-2 on Leydig cell steroidogenesis are developmentally regulated and stage-specific.
• Heparan sulfate proteoglycans (HSPG) are essential mediators of FGF actions in Leydig cells.
• FGF-1 and FGF-2 may play distinct roles in regulating Leydig cell function during development.