Immunohistochemical Jun/Fos protein localization and DNA synthesis in rat adrenal cortex after treatment with ACTH or FGF2

Abstract

In vitro and in vivo studies have suggested that the expression of the early response genes for Jun and Fos proteins plays an important role in adrenal cell proliferation. In order to study the expression pattern of the activating protein-1 (AP-1) family of oncogenes in the adrenal gland, we have used immunohistochemistry to localize Jun and Fos protein expression in rat adrenal cortex infused in situ with adrenocorticotropic hormone (ACTH), fibroblast growth factor 2 (FGF2), or both. The expression of AP-1 factors has been found to be correlated with in vivo ACTH and FGF2 proliferation in rats treated with dexamethasone and bromodeoxyuridine (BrdU). Induction of c-Jun and c-Fos in the zona fasciculata and of FosB in the zona reticularis suggests that, after ACTH stimulation, these proteins are the main AP-1 components in these zones. In vivo, ACTH increases BrdU-positive cells in the zona fasciculata and zona reticularis suggesting that the composition of AP-1 complexes in these zones is correlated with proliferation. Patterns of Fos and Jun induction by FGF2 do not resemble those after ACTH induction. However, in isolation, neither affects the zona glomerulosa. In the zona fasciculata, and more so in the zona reticularis, FGF2 modulates responses to ACTH, reducing the numbers of Jun-positive cells, Fos-positive cells, and DNA synthesis. This indicates that FGF2 antagonizes ACTH, and that ACTH thus controls the trophic effect independently of exogenous FGF2. Our results implicate the AP-1 family of transcription factors in the regulation of cell progression and the control of ACTH-induced proliferation in the zona fasciculata and zona reticularis.

Synthetic modified N-POMC1–28 controls in vivo proliferation and blocks apoptosis in rat adrenal cortex

“…Previous findings from our laboratory have shown that ACTH administration in hypophysectomized (Hyp) or Dextreated rats induces S-phase entry in all zones of the adrenal cortex, which confirms that the adrenocortical proliferative capacity is not restricted to the outer adrenal zone (Baccaro et al 2007;Torres and Lotfi 2007). Moreover, these studies have implicated the AP-1 family of transcription factors in the regulation of the cell cycle during ACTH-induced proliferation in the adrenal cortex .…”

“…Conversely, evidence is also available that each zone can be renewed from within itself. Although proliferation is more frequent in the subcapsular/glomerulosa cell zone, it is not restricted to this region, since cell proliferation also occurs in the ZF and ZR (McEwan et al 1999;Baccaro et al 2007;Torres and Lotfi 2007). Additionally, there is evidence that POMC-derived peptides other than ACTH play a role in the control of adrenal growth.…”

“…Dex (Aché Laboratórios Farmacêuticos, Campinas, SP, Brazil) treatment was performed as described in Baccaro et al (2007). Briefly, male Sprague-Dawley rats were divided into five groups (n=4-5): Dex+, Dex+ACTH 1-39 , Dex+N-POMC 1-28 , Dex+ACTH 1-39 +N-POMC 1-28 , and control (Dex−).…”

Histological Study of Adrenal Gland In Case Of Suicidal Deaths

“…BaccaroRB, Mendonce PO, Torres TE et al, 2007 found a growth factor FGF responsible for adrenocortical growth in response to stress. 1 According to Viard et al (1994), it was observed that ACTH blocks progression of adrenocortical cells in G1 phase and inhibits DNA synthesis in S-phase, even in the presence of growth factors. After this inhibiting effect, ACTH induces expression of genes associated with cell cycle progression such as C-fos and C-jun.…”

Chronic Stress Effects on Adrenal Cortex Cellular Proliferation in Pregnant Rats

“…This observed difference between techniques may be due to different marked cell populations. The fraction of cell nuclei marked with PCNA is the cell population in late G1, early S phase and DNA synthesis period, while BrDU is only incorporated in cells during DNA synthesis and repairing, offering more precise estimations (Connolly & Bogdanffy, 1993;Baccaro et al, 2007).…”