Increased Hepatic A6-Desaturase Activity with Growth
Hormone Expression in the MG101 Transgenic Mouse 1
Manabu T. Nakamura a,2, Stephen D. Phinney b'*, Anna B. Tang b,
Anita M. Oberbauer c, J. Bruce German a, and James D. Murray c
Departments of CAnimal Science, aFood Science & Technology, blnternal Medicine,
and Cpopulation Health and Reproduction, University of California, Davis, California
Growth hormone (GH) has many metabolic ef-
fects, but its mechanism(s) of action are not fully understood.
We studied the short-term effects of endogenously produced
GH on liver A6-desaturase activity and adipose and liver lipid
fraction fatty acid composition in transgenic mice. MG101
transgenic mice ages 73-114 d received zinc to activate the
ovine GH transgene for 7 d. Nontransgenic littermates, used as
controls, also received zinc. Liver lipids were fractionated into
phospholipids (PL), cholesteryl esters, and triglycerides (TG),
and retroperitoneal adipose fractionated into PL and TG for fatty
acid analysis. Liver microsomes were assayed for A6-desaturase
activity. Animals expressing the ovine growth hormone trans-
gene had a 2.5-fold higher liver A6-desaturase activity than con-
trols. Arachidonate and docosahexaenoate were significantly
higher in liver PL of GH transgenic animals compared to con-
trois, but both were decreased in adipose PL in the GH animals.
We conclude that increased production of GH affects both pro-
duction and organ distribution of highly unsaturated fatty acids.
The changes in arachidonate in various lipid pools following
transgene expression may mediate the systemic actions of GH.
Transgenic animals carrying growth hormone (GH) genes can
have increased lean body mass and growth, which is of po-
tential benefit to meat production. However, most of these
transgenic animal lines suffer from various side effects in-
cluding arthritis and impaired immune and reproductive func-
tions (1). The MG101 mouse carries the ovine GH (oGH)
structural gene fused with the sheep metallothionein la
(oMTla) promoter (2). With this combination, the MG101
mice have a minimal level of basal expression of oGH, but
high expression induced with 25 mM zinc in their drinking
(2). This strain of mice does not show apparent pathol-
to Dr. John E. Kinsella, who died on May 2, 1993.
Department of Human Ecology, GEA 115, University of
Texas, Austin, TX 78712.
*To whom correspondence should be addressed at Division of Clinical Nu-
trition TB-156, University of California, Davis, CA 95616.
CE, cholesteryl esters; GH, growth hormone; oMTla, ovine
metallothionein la; oGH, ovine growth hormone; PL, phospholipids; TG,
ogy after prolonged induction of GH. Nevertheless, these
mice show marked enlargement of the liver and spleen (3) in
addition to increased overall body size.
Recent studies suggest that GH stimulates hematopoiesis
and modulates immune functions, although the mechanisms
of these effects are unknown (4). Maddaiah and Clejan (5) re-
ported that GH administration to hypophysectomized rats