title: Developmental roles of the steroidogenic acute regulatory protein (StAR) as revealed by StAR knockout mice.
abstract: Steroidogenic acute regulatory protein (StAR) is essential for adrenal and gonadal steroidogenesis, stimulating the translocation of cholesterol to the inner mitochondrial membrane where steroidogenesis commences. StAR mutations in humans cause congenital lipoid adrenal hyperplasia (lipoid CAH), an autosomal recessive condition with severe deficiencies of all classes of steroid hormones. We previously described StAR knockout mice that mimic many features of lipoid CAH patients. By keeping StAR knockout mice alive with corticosteroid replacement, we now examine the temporal effects of StAR deficiency on the structure and function of steroidogenic tissues. The adrenal glands, affected most severely at birth, exhibited progressive increases in lipid deposits with aging. The testes of newborn StAR knockout mice contained scattered lipid deposits in the interstitial region, presumably in remnants of fetal Leydig cells. By 8 weeks of age, the interstitial lipid deposits worsened considerably and were associated with Leydig cell hyperplasia. Despite these changes, germ cells in the seminiferous tubules appeared intact histologically, suggesting that the StAR knockout mice retained some capacity for androgen biosynthesis. Sperm maturation was delayed, and the germ cells exhibited histological features of apoptosis, consistent with suboptimal androgen production. Immediately after birth, the ovaries of StAR knockout mice appeared normal. After the time of normal puberty, however, prominent lipid deposits accumulated in the interstitial region, accompanied by marked luteinization of stromal cells and incomplete follicular maturation that ultimately culminated in premature ovarian failure. These studies provide the first systematic evaluation of the developmental consequences of StAR deficiency in the various steroidogenic organs.
authors.affiliation: Department of Internal Medicine and Pharmacology, University of Texas Southwestern Medical Center, Dallas 75235, USA.
authors.forename: T
authors.initials: T
authors.lastname: Hasegawa
authors.forename: L
authors.initials: L
authors.lastname: Zhao
authors.forename: K M
authors.initials: KM
authors.lastname: Caron
authors.forename: G
authors.initials: G
authors.lastname: Majdic
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: S
authors.initials: S
authors.lastname: Shizawa
authors.forename: H
authors.initials: H
authors.lastname: Sasano
authors.forename: K L
authors.initials: KL
authors.lastname: Parker
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000311:Adrenal Glands / Q000166:cytology / Q000187:drug effects / Q000254:growth & development*; D000375:Aging; D000818:Animals; D003345:Corticosterone / Q000097:blood; D004958:Estradiol / Q000097:blood; D005260:Female; D020249:Hormone Replacement Therapy; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008901:Mineralocorticoids / Q000494:pharmacology; D010053:Ovary / Q000166:cytology / Q000187:drug effects / Q000254:growth & development*; D010063:Ovum / Q000502:physiology; D010750:Phosphoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011467:Prostate / Q000166:cytology / Q000254:growth & development; D012669:Seminal Vesicles / Q000166:cytology / Q000254:growth & development; D013094:Spermatozoa / Q000502:physiology; D013737:Testis / Q000166:cytology / Q000187:drug effects / Q000254:growth & development*; D013739:Testosterone / Q000097:blood; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D000305:Adrenal Cortex Hormones; D008565:Membrane Proteins; D008901:Mineralocorticoids; D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D013739:Testosterone; D004958:Estradiol; D003345:Corticosterone