Adrenal Function in females with low plasma HDL-C due to mutations in ABCA1 and LCAT.
BACKGROUND
Adrenal steroidogenesis is essential for human survival and depends on the availability of the precursor cholesterol. Male subjects with low plasma levels of high density lipoprotein (HDL) cholesterol are characterized by decreased adrenal function. Whether this is also the case in female subjects with low plasma HDL-C levels is unresolved to date.


RESULTS
15 female ATP binding cassette transporter AI (ABCAI) and 14 female lecithin-cholesterol acyltransferase (LCAT) were included in the study. HDL-C levels were 38% and 41% lower in ABCA1 and LCAT mutation carriers compared to controls, respectively. Urinary steroid excretion of 17-ketogenic steroids or 17-hydroxy corticosteroids did not differ between 15 female ABCA1 mutation carriers (p = 0.27 vs 0.30 respectively) and 30 matched normolipidemic controls or between 14 female LCAT mutation carriers and 28 matched normolipidemic controls (p = 0.10 and 0.14, respectively). Cosyntropin testing in an unselected subgroup of 8 ABCA1 mutation carriers and 3 LCAT mutation carriers did not reveal differences between carriers and controls.


CONCLUSIONS
Adrenal function in females with molecularly defined low HDL-C levels is not different from controls. The discrepancy with the finding of impaired steroidogenesis in males with molecularly defined low HDL-C levels underscores the importance of gender specific analyses in cholesterol-related research.
Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
Andrea E
AE
Bochem
Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
Adriaan G
AG
Holleboom
Department of Medicine, Academic Medical Center, Amsterdam, The Netherlands.
Johannes A
JA
Romijn
Leiden/Amsterdam Center for Drug Research, Leiden, The Netherlands.
Menno
M
Hoekstra
Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands; Department of Experimental Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
Geesje M
GM
Dallinga
Department of Experimental Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
Mahdi M
MM
Motazacker
Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
G Kees
GK
Hovingh
Department of Pathology & Medical Biology, Medical Biology Section, Molecular Genetics, University Medical Center Groningen, University of Groningen, The Netherlands.
Jan A
JA
Kuivenhoven
Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
Erik S G
ES
Stroes
D015068:17-Ketosteroids / Q000378:metabolism; D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics*; D000311:Adrenal Glands / Q000378:metabolism*; D000328:Adult; D008076:Cholesterol, HDL / Q000378:metabolism*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000235:genetics / Q000378:metabolism*
D015068:17-Ketosteroids; C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D008076:Cholesterol, HDL; D007862:Phosphatidylcholine-Sterol O-Acyltransferase