Adrenal neutral cholesteryl ester hydrolase: identification, subcellular distribution, and sex differences

Area of Science:

• Endocrinology
• Biochemistry
• Molecular Biology

Background:

• Adrenal glands exhibit significant neutral cholesteryl ester hydrolase (CEH) activity.
• Male rats display higher CEH activity than females.
• The specific enzymes and reasons for sex-based differences in adrenal CEH activity remain unidentified.

Purpose of the Study:

• To identify the enzyme responsible for neutral CEH activity in adrenal glands.
• To investigate the basis for sex differences in adrenal CEH activity.

Main Methods:

• Utilized hormone-sensitive lipase (HSL) knockout (HSL-/-) mice to assess CEH activity.
• Examined adrenal tissue from rats using mechanical separation and subcellular fractionation.
• Analyzed HSL protein expression and CEH activity in different adrenal fractions and sexes.

Main Results:

• In HSL-/- mice, neutral CEH activity was reduced by over 98% compared to controls.
• Female HSL-/- mice exhibited diminished stimulated corticosterone levels.
• Immunoreactive HSL was predominantly found in the microsomal fraction of rat adrenal cells.
• Microsomal fractions showed significantly higher neutral CEH activity (4-10 fold) than other cellular fractions.
• No sex-based differences in HSL protein expression or distribution were observed.
• Female adrenals had lower microsomal CEH activity and higher cholesteryl ester content.

Conclusions:

• Hormone-sensitive lipase (HSL) accounts for the majority of neutral CEH activity in adrenal glands.
• HSL is primarily localized to the microsomal fraction within adrenal cells.
• Adrenal CEH activity is modulated by sex, with females exhibiting lower activity and higher cholesteryl ester accumulation.