It has been shown that growth hormone (GH) and insulin-like growth factor-1 (IGF1) enhance steroidogenesis responsiveness to ACTH in cultured adrenal cells. To investigate the GH effect on adrenal steroidogenesis in non-GH-deficient subjects, we studied 9 girls with Turner syndrome (chronological age 5.5–7.2 years; bone age 5–7 years). In all subjects an ACTH test (Synacthen depot, 0.25 mg i.v. with blood samples at 0 and 60  min) was performed basally at 8–9 a.m. and 6 months after GH therapy (1 IU/kg/week). 17-Hydroxypregnenolone (17PGN), 17-hydroxyprogesterone (17OHP), dehydroepiandrosterone (DHA), its sulfate (DHA-S), androstenedione and cortisol were evaluated by radioimmunoassay. Two groups of normal girls were selected as controls: group A age-matched the patients at the start of the study, and group B age-matched the patients at the end of the study. The responsiveness of each hormone to ACTH was expressed as the difference between stimulated and basal values. A p value of < 0.01 was considered to indicate significance. There were no significant differences between pre- and posttreatment basal values of 17PGN, 17OHP, DHA, androstenedione and cortisol in the Turner syndrome patients, whereas a significant increase was observed for basal DHA-S (1.57 ± 0.31; 1.89 ± 0.43 µmol/l, p < 0.01). Comparison of increments before and after GH treatment showed a significant increase in responsiveness to ACTH after GH therapy DHA (p < 0.01). The increase in 17PGN was evident (p < 0.02), but the established significant p value was not reached. No differences for 17OHP, androstenedione and cortisol were found. The stimulated 17PGN/17OHP ratio was significantly higher (p < 0.01) after GH, whereas the 17OHP/androstenedione ratio was considerably lower, but the p value was < 0.02. No differences between pretreatment values with the control group androstenedione was found, whereas basal and stimulated posttreatment values of DHA and stimulated values of 17PGN were higher in patients after GH therapy than in control group B. No differences between the 2 control groups were found. In conclusion our study showed that adrenal steroid responsiveness to ACTH increases in Turner syndrome after long-term treatment with high GH doses. An increase in the number of ACTH adrenal receptors and/or a modulation of enzyme activities may be suggested. The positive or negative pharmacological implications of these data remain to be determined especially when taking into consideration the wide use of GH therapy in non-GH-deficient subjects.

Keywords:
Growth hormone, Turner syndrome, Adrenal steroidogenesis, ACTH test
1.
Giudice LC: Insulin-like growth factors and ovarian follicular development. Endocr Rev 1992;13:641–668.
2.
Skinner MK: Cell-cell interactions in the testis. Endocr Rev 1991;12:45–77.
3.
Penhoat A, Saez JM: Cultured adrenal cells are the site of action and secretion of insulin-like growth factor I (IGF-I). Cell Mol Biol 1992;222:273–281.
4.
Pillion DJ, Arnold P, Yang M, Stockard CR, Grizzle WE: Receptors for insulin and insulin-like growth factor I in the human adrenal gland. Biochem Biophys Res Commun 1989;165:204–211.
5.
Bianchi P, Concolino G, Adamo MV, Rombolà N, Palma E, Monti S, Toscano V: Effects of some peptides on adrenal cells of fasciculata-granulosa (F-G) in primary culture (abstract C134). Proc 9th Int Congr on Hormonal Steroids, 1994.
6.
Bianchi P, Toscano V, Monaco G, Marano G, Lubrano C, Sciarra F: Effects of ACTH, insulin and insulin-like growth factor I on guinea pig adrenals fasciculata-glomerulosa cells (abstract). J Endocrinol Invest 1993;16(suppl 1):88.
7.
Toscano V, Balducci R, Adamo MV, Mangiantini A, Cives C, Boscherini B: Changes in steroid pattern following acute and chronic adrenocorticotropin administration in premature adrenarche. J Steroid Biochem 1989;32:321–326.
8.
Toscano V, Adamo MV, Caiola S, Foli S, Petrangeli E, Casilli D, Sciarra F: Is hirsutism an evolving syndrome? J Endocrinol 1983;97:379–387.
9.
Toscano V, Petrangeli E, Adamo MV, Foli S, Caiola S, Sciarra F: Simultaneous determination of 5a reduced metabolites of testosterone in human plasma. J Steroid Biochem 1981;14:574–578.
10.
Balducci R, Boscherini B, Mangiantini A, Morellini M, Toscano V: Isolated precocious pubarche: An approach. J Clin Endocrinol Metab 1994;79:582–589.
11.
Larizza D, Cuccia M, Martinetti M, Maghnie M, Dondi E, Salvaneschi L, Severi F: Adrenocorticotrophin stimulation and HLA polymorphism suggest a high frequency of heterozygosity for steroid 21-hydroxylase deficiency in patients with Turner’s syndrome and their families. Clin Endocrinol 1994;40:39–45.
12.
David R, Landin I, Druker W: Plasma dehydroepiandrosterone-sulfate in hypothalamic-pituitary disfunction; in Gennazzani AR, Thijssen JMH, Siiteri PK (eds): Adrenal Androgens. New York, Raven Press, 1980, pp 309–314.
13.
Cohen HN, Beastall GH, Wallace AM, Fogelman I, Thomson JA: Clinical value of adrenal androgen measurement in the diagnosis of delayed puberty. Lancet 1981;i:689–692.
14.
Sklar CA, Ulstrom RA: Effect of human growth hormone on adrenal androgens in children with growth hormone deficiency. Horm Res 1984;20:166–171.
15.
Hondo MM, Vanderschueren-Lodeweyckx M, Vlietnick R: Plasma androgens in children and adolescent. II. A longitudinal study in patients with hypopituitarism. Horm Res 1982;16:78–95.
16.
Castro-Magana M, Maddaiah VT, Collip PJ, Angulo M: Synergistic effects of growth hormone therapy on plasma levels of 11-deoxycortisol and cortisol in growth hormone-deficient children. J Clin Endocrinol Metab 1983;56:662–667.
17.
Merola B, Rossi E, Colao A, et al: Effect of a short-term treatment with recombinant growth hormone (GH) on adrenal responsiveness to corticotrophin stimulation in children affected by isolated GH deficiency. J Clin Endocrinol Metab 1992;74:1210–1214.
18.
Rossi E, Merola B, Longobardi S, Esposito V, Tommaselli AP, Colao A, et al: Acute and chronic effects of human recombinant GH (hrGH) on adrenal steroidogenesis in children affected with isolated GH deficiency (IGHD). J Clin Endocrinol Metab 1995; 80:2251–2254.
19.
Penhoat A, Jaillard C, Saez JM: Synergistic effects of corticotropin and insulin-like growth factor I on corticotropin receptors and corticotropin responsiveness in cultured bovine adrenocortical cells. Biochem Biophys Res Commun 1989;165:355–359.
20.
Balducci R, Toscano V, Mangiantini A, Bianchi P, Guglielmi R, Boscherini B: The effect of growth hormone administration on testicular response during gonadotropin therapy in subjects with combined gonadotropin and growth hormone deficiencies. Acta Endocrinol 1993;128:19–23.
21.
Rich BH, Rosenfield RL, Lucky AW, Helke JC, Otto P: Adrenarche: Changing adrenal response to adrenocorticotropin. J Clin Endocrinol Metab 1981;52:1129–1136.
1998
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