THE EPISODIC SECRETORY PATTERN OF GROWTH-HORMONE REGULATES LIVER CARBONIC ANHYDRASE-III - STUDIES IN NORMAL AND MUTANT GROWTH-HORMONE-DEFICIENT DWARF RATS

Carbonic anhydrase III (CAIII) occurs in male rat liver at concentrations twenty times those in the female, and is sensitive to the pattern of growth hormone (GH) release. Males release GH episodically and have high concentrations of CAIII; females produce GH in a more continuous fashion and have lower CAIII levels. In normal female rats, the endogenous GH secretory pattern was masculinized, either by regular injections of GH-releasing factor (GRF) or by intermittent infusions of somatostatin (90 min on/90 min off). Both treatments induced regular GH pulses and stimulated growth, but only intermittent somatostatin infusions raised CAIII levels (controls, 1.5 ± 0.5; somatostatin-treated, 9.0 ± 2.9 μg/mg; means ± S.D.). GRF pulses (4 μg every 4 h) did not however raise CAIII levels (controls 1.8 ± 0.5; GRF-treated 1.4 ± 0.4 μg/mg). Surprisingly, hepatic CAIII is also sexually dimorphic (males, 18.8 ± 3; females, 2.22 ± 0.4 μg/mg) in a GH-deficient dwarf rat strain which has low plasma GH levels without 3-hourly GH peaks. Intermittent somatostatin infusions in female dwarf rats partially masculinized hepatic CAIII, an effect reduced by coinfusion with GRF. This CAIII response was not secondary to growth induction, since neither somatostatin nor GRF stimulated growth in dwarf rats, and pulses of exogenous GH stimulated growth in female dwarfs without masculinizing CAIII levels. Furthermore, continuous GH infusion in male dwarf rats partially feminized hepatic CAIII levels (to 9.1 ± 2.4 μg/mg), whereas infusions of insulin-like growth factor-1, which induced the same body weight gain, did not affect hepatic CAIII (20.8 ± 6 μg/mg). These results show that hepatic CAIII expression is highly sensitive to the endogenous GH secretory pattern, independent of growth. They also implicate the low basal GH levels between pulse, rather than the peak GH levels, as the primary determinant of the sexually dimorphic hepatic CAIII expression in the rat.