Gonadotropin-regulated long chain
fatty acid Acyl-CoA synthetase (GR-LACS), is a member of the LACS family that is regulated by
gonadotropin in the rat Leydig cell (LC). Its mouse/human homologs,
lipidosin/bubblegum, have been suggested to participate in
X-linked adrenoleukodystrophy (
X-ALD), an adreno/
neurodegenerative disorder with accumulation of very long chain
fatty acids (VLCFA) in tissues and plasma. To further gain insights into its regulatory function, a GR-LACS/
lipidosin null mouse was generated. No apparent phenotypic abnormalities were observed in the
X-ALD target tissues (brain, testis, adrenal). Nuclear inclusions seen in mice >15 month-old, were present in LC of 9 month-old GR-LACS(-/-) mice. LC of the null mice showed refractoriness to the
gonadotropin-induced desensitization of
testosterone production that is observed in adult animals. LCFAs were moderately increased in the testis, ovary and brain, but not in the adrenal gland of GR-LACS(-/-) mice, with no major changes in VLCFA. No change in LACS activity was observed in these tissues, suggesting a compensatory mechanism exhibited by other LACS members. The GR-LACS(-/-) model did not support its association with
X-ALD. These studies revealed a role of GR-LACS in reducing the aging process of the LC, and its participation in
gonadotropin-induced testicular desensitization of
testosterone production.