Cholesterol transport into mitochondria is the rate-limiting step for de novo steroid hormone synthesis, such as that of progesterone.  In women, ovarian progesterone is needed for normal menstrual cycles and supporting early pregnancy.  This rate-limiting step is carried out by Steroidogenic Acute Regulatory Protein also known as StAR or STARD1, which has a cholesterol binding domain now called the START domain.  The characterization of STARD1 gave rise to the discovery of a family of START domain proteins. Two of these novel proteins are non-vesicular cholesterol transporters STARD4 and STARD6.

In a recently published study by Holly LaVoie, Professor, at the USC School of Medicine Columbia, she and her lab showed that in addition to STARD1, STARD4 and STARD6 transcripts are expressed in human primary ovarian steroidogenic cells.  STARD4, rather than STARD6, was the major protein produced and present at high levels in steroidogenic cells and human ovarian tissue.  STARD4 transcripts were increased by protein kinase A and C agonists and decreased by excess cholesterol.

In human ovarian cells, STARD4, but not STARD6, has the potential to provide cholesterol for STARD1-mediated progesterone production.

This research article is part of the 30 years of StAR: Anniversary Collection of the Journal of Endocrinology.

Differential regulation of STARD1, STARD4 and STARD6 in the human ovary.

Yahya NA, King SR, Shi B, Shaaban A, Whitfield NE, Yan C, Kordus RJ, Whitman-Elia GF, LaVoie HA. J Endocrinol. 2024 Jul 3;262(2):e230385. doi: 10.1530/JOE-23-0385. Print 2024 Aug 1. PMID: 38829257