Do estrogens regulate lipid status in testicular steroidogenic Leydig cell?

Area of Science:

• Endocrinology
• Cell Biology
• Reproductive Biology

Background:

• Estrogen plays a critical role in regulating Leydig cell function.
• Membrane estrogen receptors, like G-protein coupled estrogen receptor (GPER), are involved in rapid cellular responses.
• Understanding estrogen's impact on Leydig cell lipid metabolism and steroidogenesis is crucial for reproductive health.

Purpose of the Study:

• To investigate the effects of a GPER antagonist (G-15) on mouse Leydig (MA-10) cells.
• To analyze changes in estrogen-related receptors (ERRs), steroidogenic markers, and lipid droplet dynamics.
• To elucidate the role of estrogen signaling in Leydig cell lipid homeostasis and steroid hormone production.

Main Methods:

• MA-10 cells were treated with G-15, an antagonist for G-protein coupled membrane estrogen receptor.
• Western blotting was used to assess protein expression of ERRs, LHR, 3β-HSD, PLIN, and LC3.
• Microscopic analyses (light and electron microscopy) and biochemical assays (cholesterol, cAMP, progesterone) were performed.

Main Results:

• G-15 treatment altered ERRβ and γ localization, decreasing expression of LHR, 3β-HSD, PLIN, and LC3.
• Significant changes in lipid droplet size, distribution, and ultrastructure, including signs of lipophagocytosis, were observed.
• Cholesterol content and cAMP levels remained unaffected by G-15, while progesterone secretion was not modulated by G-15, BPA, or ICI alone or in combination.

Conclusions:

• G-15 disrupts lipid homeostasis and affects steroidogenic markers in mouse Leydig cells.
• Estrogen signaling, involving GPER, ER, and ERR interactions, significantly influences Leydig cell lipid metabolism and steroidogenesis.
• Endogenous and exogenous estrogens exert complex effects on Leydig cell function through various receptor pathways.