The episodic secretory pattern of growth hormone regulates liver carbonic anhydrase III. Studies in normal and mutant growth-hormone-deficient dwarf rats

Abstract

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 micrograms/mg; means +/- S.D.). GRF pulses (4 micrograms every 4 h) did not however raise CAIII levels (controls 1.8 +/- 0.5; GRF-treated 1.4 +/- 0.4 micrograms/mg). Surprisingly, hepatic CAIII is also sexually dimorphic (males, 18.8 +/- 3; females, 2.22 +/- 0.4 micrograms/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 co-infusion 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 micrograms/mg), whereas infusions of insulin-like growth factor-1, which induced the same body weight gain, did not affect hepatic CAIII (20.8 +/- 6 micrograms/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 pulses, rather than the peak GH levels, as the primary determinant of the sexually dimorphic hepatic CAIII expression in the rat.

Growth Hormone Overexpression in the Central Nervous System Results in Hyperphagia-Induced Obesity Associated With Insulin Resistance and Dyslipidemia

“…However, most of the changes observed in Mt-bGH mice with respect to regulation of genes involved in lipid and carbohydrate metabolism are not observed in the GFAP-bGH mice (66). Together, these results indicate a change from pulsatile to continuous secretion of GH in male mice as indicated by the change in gene expression of the prolactin receptor, testosterone 16-␣ hydroxylase, 3-ketosteroid reductase, major urinary proteins, and carbonic anhydrase III (55)(56)(57)(58)67). Thus, the changed plasma pattern of GH seems to feminize the hepatic gene expression of male mice.…”

“…Further selection was done using the Incyte hierarchies of protein function and enzymes as well as the enzyme commission number. In Table 3, the difference in gene expression between GFAP-bGH transgenic mice and littermate controls is given with respect to genes involved in metabolism as well as genes dependent on the sexually dimorphic secretory pattern of growth hormone (55)(56)(57)(58). No effect on IGF1mRNA but increased GH receptor mRNA expression was observed (Table 3).…”

Influence of the high-affinity growth hormone (GH)-binding protein on plasma profiles of free and bound GH and on the apparent half-life of GH. Modeling analysis and clinical applications.

“…In contrast, in acromegaly, the nadir (or mean or integrated) serum GH concentration is the strongest single correlate of serum IGF-I concentrations (36). Moreover, the induction of a "feminized" pattern of certain hepatic enzymes (e.g., carbonic anhydrase in the rat) is best achieved by continuous GH delivery (51 ). Near-continuous GH replacement may also be optimal for generating IGF-I in GH-deficient humans (52).…”

Sexual dimorphism in LEC rat liver: Suppression of carbonic anhydrase III by copper accumulation during hepatocarcinogenesis

“…CAIII occurs in male rat liver at concentrations twenty times those in the female. Their group (11) has also shown that CAIIl expression is highly sensitive to the endogenous growth hormone secretory pattern. Males release growth hormone episodically and have high concentrations of CAIII; however females produce growth hormone in a more continuous fashion and have lower CAIII levels.…”