This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ross, J. T. Articles by McMillen, I. C. Search for Related Content PubMed PubMed Citation Articles by Ross, J. T. Articles by McMillen, I. C. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB HYDROCORTISONE

Infusion of N-Proopiomelanocortin-(1–77) Increases Adrenal Weight and Messenger Ribonucleic Acid Levels of Cytochrome P₄₅₀ 17-Hydroxylase in the Sheep Fetus during Late Gestation¹

Department of Physiology, University of Adelaide, Adelaide, South Australia 5005, Australia; and Endocrine Laboratory, Royal Victoria Hospital and Department of Medicine, McGill University (H.P.J.B., S.J.), Montréal H3T 1EJ, Québec, Canada

Address all correspondence and requests for reprints to: Prof. I. C. McMillen, Department of Physiology, University of Adelaide, Adelaide, South Australia 5005, Australia. E-mail: caroline.mcmillen{at}adelaide.edu.au

In the sheep there is a rapid increase in fetal adrenal growth and steroidogenesis during the last 10–15 days gestation (term = 147 ± 3 days gestation). In the rat, peptides derived from the N-terminal region of POMC play a role in compensatory adrenal growth and in potentiation of ACTH-induced steroidogenesis. We therefore investigated the effects of infusion of bovine N-POMC-(1–77) and its biosynthetic derivative, N-POMC-(1–49) on adrenal growth and on the expression of adrenal steroidogenic enzymes in the late gestation sheep fetus. Twenty-seven pregnant ewes were used in this study. Fetal vascular catheters were inserted between 116–125 days gestation, and purified bovine N-POMC-(1–77) (2 µg/ml·h), N-POMC-(1–49) (2 µg/ml·h) and saline were each infused for 48 h between 136 and 138 days gestation. Intrafetal infusion of N-POMC-(1–77) resulted in an increased adrenal/fetal body weight ratio (94.6 ± 5.7 mg/kg) compared with that in saline-infused (75.6 ± 1.8 mg/kg), but not N-POMC-(1–49)-infused (82.7 ± 6.1 mg/kg), fetal sheep. The ratio of CYP17 messenger RNA (mRNA) to 18S ribosomal RNA was also significantly higher in fetal adrenals of the N-POMC-(1–77)-infused group (49.1 ± 4.7) compared with that in either the N-POMC-(1–49)-infused (20.4 ± 6.4) or saline-infused (15.2 ± 4.4) group. There was no difference, however, in the ratios of adrenal CYP11A1 mRNA/3ß- hydroxysteroid dehydrogenase/⁵,⁴-isomerase mRNA and CYP21A1 mRNA/18S ribosomal RNA among the N-POMC-(1–77)-, N-POMC-(1–49)-, and saline-infused groups. There was also no significant change in either plasma cortisol or ACTH concentrations in response to the infusion of either N-POMC-(1–77) or N-POMC-(1–49). In summary, intrafetal infusion of N-POMC-(1–77) stimulated fetal adrenal growth and resulted in a specific increase in adrenal CYP17 gene expression in late gestation. N-POMC-(1–77) may therefore play a modulatory role in the increase in fetal adrenal growth and steroidogenesis that occurs before birth.

This article has been cited by other articles:

				J. T. Ross, I. C. McMillen, F. Lok, A. G. Thiel, J. A. Owens, and C. L. Coulter Intrafetal Insulin-Like Growth Factor-I Infusion Stimulates Adrenal Growth But Not Steroidogenesis in the Sheep Fetus during Late Gestation Endocrinology, November 1, 2007; 148(11): 5424 - 5432. [Abstract] [Full Text] [PDF]

				K.E. Warnes, I.C. McMillen, J.S. Robinson, and C.L. Coulter Differential Actions of Metyrapone on the Fetal Pituitary-Adrenal Axis in the Sheep Fetus in Late Gestation Biol Reprod, August 1, 2004; 71(2): 620 - 628. [Abstract] [Full Text] [PDF]

				M. Fassnacht, S. Hahner, I. A. Hansen, T. Kreutzberger, M. Zink, K. Adermann, F. Jakob, J. Troppmair, and B. Allolio N-Terminal Proopiomelanocortin Acts as a Mitogen in Adrenocortical Tumor Cells and Decreases Adrenal Steroidogenesis J. Clin. Endocrinol. Metab., May 1, 2003; 88(5): 2171 - 2179. [Abstract] [Full Text] [PDF]

				F. Beuschlein, C. Mutch, D. L. Bavers, Y. M. Ulrich-Lai, W. C. Engeland, C. Keegan, and G. D. Hammer Steroidogenic Factor-1 Is Essential for Compensatory Adrenal Growth Following Unilateral Adrenalectomy Endocrinology, August 1, 2002; 143(8): 3122 - 3135. [Abstract] [Full Text] [PDF]