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.
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- Baxter R. C., Bryson J. M., Turtle J. R. Somatogenic receptors of rat liver: regulation by insulin. Endocrinology. 1980 Oct;107(4):1176–1181. doi: 10.1210/endo-107-4-1176. [DOI] [PubMed] [Google Scholar]
- Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
- Carter N. D., Hewett-Emmett D., Jeffrey S., Tashian R. E. Testosterone-induced, sulfonamide-resistant carbonic anhydrase isozyme of rat liver is indistinguishable from skeletal muscle carbonic anhydrase III. FEBS Lett. 1981 Jun 1;128(1):114–118. doi: 10.1016/0014-5793(81)81094-0. [DOI] [PubMed] [Google Scholar]
- Charlton H. M., Clark R. G., Robinson I. C., Goff A. E., Cox B. S., Bugnon C., Bloch B. A. Growth hormone-deficient dwarfism in the rat: a new mutation. J Endocrinol. 1988 Oct;119(1):51–58. doi: 10.1677/joe.0.1190051. [DOI] [PubMed] [Google Scholar]
- Chatterjee B., Demyan W. F., Gustafsson J. A., Harris M. W., Hökfelt T., Norstedt G., Roy A. K. Effect of anterior hypothalamic deafferentation and continuous growth hormone infusion on the hepatic synthesis of alpha 2u-globulin in the male rat. J Endocrinol. 1986 Mar;108(3):351–355. doi: 10.1677/joe.0.1080351. [DOI] [PubMed] [Google Scholar]
- Clark R. G., Carlsson L. M., Rafferty B., Robinson I. C. The rebound release of growth hormone (GH) following somatostatin infusion in rats involves hypothalamic GH-releasing factor release. J Endocrinol. 1988 Dec;119(3):397–404. doi: 10.1677/joe.0.1190397. [DOI] [PubMed] [Google Scholar]
- Clark R. G., Carlsson L. M., Robinson I. C. Growth hormone secretory profiles in conscious female rats. J Endocrinol. 1987 Sep;114(3):399–407. doi: 10.1677/joe.0.1140399. [DOI] [PubMed] [Google Scholar]
- Clark R. G., Chambers G., Lewin J., Robinson I. C. Automated repetitive microsampling of blood: growth hormone profiles in conscious male rats. J Endocrinol. 1986 Oct;111(1):27–35. doi: 10.1677/joe.0.1110027. [DOI] [PubMed] [Google Scholar]
- Clark R. G., Jansson J. O., Isaksson O., Robinson I. C. Intravenous growth hormone: growth responses to patterned infusions in hypophysectomized rats. J Endocrinol. 1985 Jan;104(1):53–61. doi: 10.1677/joe.0.1040053. [DOI] [PubMed] [Google Scholar]
- Clark R. G., Robinson I. C. Growth hormone responses to multiple injections of a fragment of human growth hormone-releasing factor in conscious male and female rats. J Endocrinol. 1985 Sep;106(3):281–289. doi: 10.1677/joe.0.1060281. [DOI] [PubMed] [Google Scholar]
- Clark R. G., Robinson I. C. Growth induced by pulsatile infusion of an amidated fragment of human growth hormone releasing factor in normal and GHRF-deficient rats. Nature. 1985 Mar 21;314(6008):281–283. doi: 10.1038/314281a0. [DOI] [PubMed] [Google Scholar]
- Clark R. G., Robinson I. C. Paradoxical growth-promoting effects induced by patterned infusions of somatostatin in female rats. Endocrinology. 1988 Jun;122(6):2675–2682. doi: 10.1210/endo-122-6-2675. [DOI] [PubMed] [Google Scholar]
- Edén S. Age- and sex-related differences in episodic growth hormone secretion in the rat. Endocrinology. 1979 Aug;105(2):555–560. doi: 10.1210/endo-105-2-555. [DOI] [PubMed] [Google Scholar]
- Garg L. C. Induction of hepatic carbonic anhydrase by estrogen. J Pharmacol Exp Ther. 1975 Feb;192(2):297–302. [PubMed] [Google Scholar]
- Gustafsson J. A., Mode A., Norstedt G., Skett P. Sex steroid induced changes in hepatic enzymes. Annu Rev Physiol. 1983;45:51–60. doi: 10.1146/annurev.ph.45.030183.000411. [DOI] [PubMed] [Google Scholar]
- Heath R., Jeffery S., Carter N. Radioimmunoassay of human muscle carbonic anhydrase III in dystrophic states. Clin Chim Acta. 1982 Mar 12;119(3):299–305. doi: 10.1016/0009-8981(82)90343-6. [DOI] [PubMed] [Google Scholar]
- Isgaard J., Carlsson L., Isaksson O. G., Jansson J. O. Pulsatile intravenous growth hormone (GH) infusion to hypophysectomized rats increases insulin-like growth factor I messenger ribonucleic acid in skeletal tissues more effectively than continuous GH infusion. Endocrinology. 1988 Dec;123(6):2605–2610. doi: 10.1210/endo-123-6-2605. [DOI] [PubMed] [Google Scholar]
- Isgaard J., Nilsson A., Lindahl A., Jansson J. O., Isaksson O. G. Effects of local administration of GH and IGF-1 on longitudinal bone growth in rats. Am J Physiol. 1986 Apr;250(4 Pt 1):E367–E372. doi: 10.1152/ajpendo.1986.250.4.E367. [DOI] [PubMed] [Google Scholar]
- Jansson J. O., Edén S., Isaksson O. Sexual dimorphism in the control of growth hormone secretion. Endocr Rev. 1985 Spring;6(2):128–150. doi: 10.1210/edrv-6-2-128. [DOI] [PubMed] [Google Scholar]
- Jansson J. O., Ekberg S., Isaksson O., Mode A., Gustafsson J. A. Imprinting of growth hormone secretion, body growth, and hepatic steroid metabolism by neonatal testosterone. Endocrinology. 1985 Nov;117(5):1881–1889. doi: 10.1210/endo-117-5-1881. [DOI] [PubMed] [Google Scholar]
- Jeffery S., Carter N. D., Wilson C. A. Hypophysectomy abolishes sexual dimorphism of liver carbonic anhydrase III. FEBS Lett. 1984 Sep 17;175(1):129–130. doi: 10.1016/0014-5793(84)80584-0. [DOI] [PubMed] [Google Scholar]
- Jeffery S., Wilson C. A., Mode A., Gustafsson J. A., Carter N. D. Effects of hypophysectomy and growth hormone infusion on rat hepatic carbonic anhydrases. J Endocrinol. 1986 Jul;110(1):123–126. doi: 10.1677/joe.0.1100123. [DOI] [PubMed] [Google Scholar]
- Leung D. W., Spencer S. A., Cachianes G., Hammonds R. G., Collins C., Henzel W. J., Barnard R., Waters M. J., Wood W. I. Growth hormone receptor and serum binding protein: purification, cloning and expression. Nature. 1987 Dec 10;330(6148):537–543. doi: 10.1038/330537a0. [DOI] [PubMed] [Google Scholar]
- MacGeoch C., Morgan E. T., Gustafsson J. A. Hypothalamo-pituitary regulation of cytochrome P-450(15) beta apoprotein levels in rat liver. Endocrinology. 1985 Nov;117(5):2085–2092. doi: 10.1210/endo-117-5-2085. [DOI] [PubMed] [Google Scholar]
- Mode A., Gustafsson J. A., Jansson J. O., Edén S., Isaksson O. Association between plasma level of growth hormone and sex differentiation of hepatic steroid metabolism in the rat. Endocrinology. 1982 Nov;111(5):1692–1697. doi: 10.1210/endo-111-5-1692. [DOI] [PubMed] [Google Scholar]
- Mode A., Norstedt G., Simic B., Eneroth P., Gustafsson J. A. Continuous infusion of growth hormone feminizes hepatic steroid metabolism in the rat. Endocrinology. 1981 Jun;108(6):2103–2108. doi: 10.1210/endo-108-6-2103. [DOI] [PubMed] [Google Scholar]
- Norstedt G., Mode A., Hökfelt T., Eneroth P., Elde R., Ferland L., Labrie F., Gustafsson J. A. Possible role of somatostatin in the regulation of the sexually differentiated steroid metabolism and prolactin receptor in rat liver. Endocrinology. 1983 Mar;112(3):1076–1090. doi: 10.1210/endo-112-3-1076. [DOI] [PubMed] [Google Scholar]
- Norstedt G., Palmiter R. Secretory rhythm of growth hormone regulates sexual differentiation of mouse liver. Cell. 1984 Apr;36(4):805–812. doi: 10.1016/0092-8674(84)90030-8. [DOI] [PubMed] [Google Scholar]
- Noshiro M., Negishi M. Pretranslational regulation of sex-dependent testosterone hydroxylases by growth hormone in mouse liver. J Biol Chem. 1986 Dec 5;261(34):15923–15927. [PubMed] [Google Scholar]
- Roy A. K., Chatterjee B. Sexual dimorphism in the liver. Annu Rev Physiol. 1983;45:37–50. doi: 10.1146/annurev.ph.45.030183.000345. [DOI] [PubMed] [Google Scholar]
- Schwander J. C., Hauri C., Zapf J., Froesch E. R. Synthesis and secretion of insulin-like growth factor and its binding protein by the perfused rat liver: dependence on growth hormone status. Endocrinology. 1983 Jul;113(1):297–305. doi: 10.1210/endo-113-1-297. [DOI] [PubMed] [Google Scholar]
- Shiels A., Jeffery S., Phillips I. R., Shephard E. A., Wilson C. A., Carter N. D. Sexual differentiation of rat liver carbonic anhydrase III. Biochim Biophys Acta. 1983 Nov 8;760(3):335–342. doi: 10.1016/0304-4165(83)90370-7. [DOI] [PubMed] [Google Scholar]
- Skottner A., Clark R. G., Fryklund L., Robinson I. C. Growth responses in a mutant dwarf rat to human growth hormone and recombinant human insulin-like growth factor I. Endocrinology. 1989 May;124(5):2519–2526. doi: 10.1210/endo-124-5-2519. [DOI] [PubMed] [Google Scholar]
- Smith W. C., Linzer D. I., Talamantes F. Detection of two growth hormone receptor mRNAs and primary translation products in the mouse. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9576–9579. doi: 10.1073/pnas.85.24.9576. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tannenbaum G. S., Martin J. B. Evidence for an endogenous ultradian rhythm governing growth hormone secretion in the rat. Endocrinology. 1976 Mar;98(3):562–570. doi: 10.1210/endo-98-3-562. [DOI] [PubMed] [Google Scholar]
