Endocrine Abstracts

The corpus luteum, a transient endocrine organ, is the major source of progesterone, the essential hormone of pregnancy. It also secretes estradiol and metabolites of both progesterone and estrogen. Furthermore, the corpus luteum produces angiogenic factors, prostaglandins and relaxin. Luteinizing hormone (LH) is of major importance in regulating corpus luteum structure and function. It stimulates ovulation and differentiation of follicular granulosa and theca cells into steroidogenic luteal cells. During the early luteal phase, endothelial cells within the corpus luteum proliferate to establish a rich capillary network critical for the delivery of gonadotropins and precursors for progesterone production. LH is responsible for maintenance of luteal function and progesterone biosynthesis. Here we summarize recent progress towards understanding cellular and organelle-specific changes induced by LH in steroidogenic luteal cells. LH activates a protein kinase A (PKA)-hormone-sensitive lipase (HSL) signaling pathway. A dynamic relationship has been established among AMP Kinase, PKA, HSL, and lipid droplets (LD) in luteal progesterone synthesis. Analysis of the LD proteome following activation of PKA revealed increased association of active HSD3B with LD. LH via PKA also acutely regulates mitochondrial (Mito) dynamics via phosphorylation of dynamin-related protein 1 (DRP1), decreasing the association of DRP1 with Mito and stimulating Mito fusion. Inhibition of DRP1 of association with Mito elevates LH-induced progesterone biosynthesis. LH also rapidly induces changes in key metabolic pathways including glycolysis, tricarboxylic acid cycle, pentose phosphate pathway, de novo lipogenesis, and hydrolysis of phospholipids. LH via PKA signaling regulates the phosphorylation/activation of acetyl-CoA carboxylase (ACACA) and ATP citrate lyase (ACLY), enzymes involved in de novo synthesis of fatty acids. Inhibition of ACLY and fatty acid transport to mitochondria suppresses LH-stimulated progesterone production. In summary, LH-sensitive metabolic pathways are essential for maintaining steroidogenesis in the corpus luteum.