Effects of prolonged cholecystokinin administration on rat pituitary-adrenocortical axis: Role of the CCK receptor subtypes 1 and 2

  • Authors:
    • Ludwik K. Malendowicz
    • Raffaella Spinazzi
    • Mariola Majchrzak
    • Magdalena Nowak
    • Gastone G. Nussdorfer
    • Agnieszka Ziolkowska
    • Carlo Macchi
    • Marcin Trejter
  • View Affiliations

  • Published online on: December 1, 2003     https://doi.org/10.3892/ijmm.12.6.903
  • Pages: 903-909
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Abstract

Many lines of evidence indicate that cholecystokinin (CCK) and its receptors, named CCK1-R and CCK2-R, are expressed in the hypothalamo-pituitary-adrenal (HPA) axis, the function of which they acutely stimulate. However, the role of endogenous CCK system in the regulation of HPA axis is still unknown. To address this issue we investigated the effect of the prolonged (6-day) administration of CCK, CCK-R antagonists (CCK-RAs) and pentagastrin (PG), a CCK2-R agonist, on adult rat HPA axis. Semiquantitative reverse transcription-polymerase chain reaction showed that CCK treatment lowered the expression of CCK1-R and CCK2-R mRNAs in the pituitary, but not adrenal gland. ACTH plasma concentration was not affected by any treatment. Neither CCK nor PG administration induced significant changes in the blood levels of aldosterone and corticosterone. CCK1-RA, although being per se ineffective, in the presence of CCK raised plasma levels of aldosterone and corticosterone; conversely, CCK2-RA, either alone or in the presence of agonists, lowered the blood concentrations of the two hormones. CCK, but not PG, treatment decreased relative adrenal weight, and morphometry showed that CCK-induced adrenal atrophy was coupled to decreases in the volume of adrenocortical zones, which in turn mainly depended on the lowering in the volume and number of adrenocortical cells. PG administration raised and CCK2-RA per se decreased the volume and number of adrenocortical cells. Taken together, these findings allow us to draw the following main conclusions: i) the prolonged exposure to elevated CCK concentrations down-regulates CCK-R expression in the pituitary gland, which accounts for the lack of effect of CCK on ACTH secretion; ii) adrenal CCK1-Rs and CCK2-Rs inhibit and stimulate, respectively, corticosteroid secretion; and iii) endogenous CCK system plays a minor role in the physiological regulation of rat HPA axis, its main effect being the CCK2-R-mediated maintenance of adrenocortical-cell number.

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December 2003
Volume 12 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Malendowicz LK, Spinazzi R, Majchrzak M, Nowak M, Nussdorfer GG, Ziolkowska A, Macchi C and Trejter M: Effects of prolonged cholecystokinin administration on rat pituitary-adrenocortical axis: Role of the CCK receptor subtypes 1 and 2. Int J Mol Med 12: 903-909, 2003
APA
Malendowicz, L.K., Spinazzi, R., Majchrzak, M., Nowak, M., Nussdorfer, G.G., Ziolkowska, A. ... Trejter, M. (2003). Effects of prolonged cholecystokinin administration on rat pituitary-adrenocortical axis: Role of the CCK receptor subtypes 1 and 2. International Journal of Molecular Medicine, 12, 903-909. https://doi.org/10.3892/ijmm.12.6.903
MLA
Malendowicz, L. K., Spinazzi, R., Majchrzak, M., Nowak, M., Nussdorfer, G. G., Ziolkowska, A., Macchi, C., Trejter, M."Effects of prolonged cholecystokinin administration on rat pituitary-adrenocortical axis: Role of the CCK receptor subtypes 1 and 2". International Journal of Molecular Medicine 12.6 (2003): 903-909.
Chicago
Malendowicz, L. K., Spinazzi, R., Majchrzak, M., Nowak, M., Nussdorfer, G. G., Ziolkowska, A., Macchi, C., Trejter, M."Effects of prolonged cholecystokinin administration on rat pituitary-adrenocortical axis: Role of the CCK receptor subtypes 1 and 2". International Journal of Molecular Medicine 12, no. 6 (2003): 903-909. https://doi.org/10.3892/ijmm.12.6.903