Structure and dynamics of adrenal mitochondria following stimulation with corticotropin releasing hormone

Abstract

The mitochondria of rat adrenals were investigated qualitatively and quantitatively in different functional states of the adrenal cortex. Following stimulation of the animals with corticotropin releasing hormone (CRH), the corticosterone serum levels reached a maximum 1 hour after stimulation with CRH. The amount of inner mitochondrial membrane within the zona fasciculata increased showing a biphasic time course, with a first maximum 2 hours and a second maximum 8 hours after stimulation. In contrast, a significant rise of mitochondrial volume occurred only 24 hours after CRH stimulation. Therefore, the dense vesicularization of mitochondrial cristae may constitute an early process to enhance the steroidogenic capacity of these cells. Within cells of the transition zone between zona glomerulosa and zona fasciculata, we could depict a special type of mitochondria with characteristic crescent-like cristae only seen after stimulation with CRH. This type of mitochondria may represent an intermediate form between mitochondria of zona glomerulosa and zona fasciculata underlining the impressive transformational capacity of adrenocortical mitochondria. After hypophysectomy, zona fasciculata cells contained mitochondria with tubular inner membranes, representing a hypofunctional state. In contrast, the hypofunctional state after hypophysectomy and the hyperfunctional state after stimulation of the adrenal cortex via CRH injection did not appear to correlate with the morphology of mitochondria from the zona reticularis and adrenal medulla.

Expression of Manganese Superoxide Dismutase mRNA in the Rat Adrenal Cortex is Associated with the Occurrence of Mitochondrial Vesicular Cristae.

“…The high expression of Mn-SOD mRNA in the zona fasciculata and reticularis, and its low expression in the zona glomerulosa of the rat adrenal cortex are consistent with the morphology of their mitochondria [13,14]. It has been reported that densely arranged vesicular cristae, representing the active state of fasciculate cells in normal rats, were transformed into a scarce tubulo-vesicular form, representing their inactive or hypo-functional state, by hypophysectomy [1,2,5,6,13,14]. However, the expression of Mn-SOD mRNA in the remaining part of the cortex in hypophysectomized rats was still higher than in hepatocytes of normal rats.…”

Restoration of adrenal steroidogenesis by adenovirus-mediated transfer of human cytochromeP450 21-hydroxylase into the adrenal gland of21-hydroxylase-deficient mice

“…The mitochondrial abnormalities in 21-OH-deficient mice resemble those described in humans with CAH, 18 and differ from the increase in mitochondrial vesicular membranes that occurs following ACTH or CRH administration. 19,20 The remarkable improvement of adrenal structure and function after gene therapy contrasts with the lack of change observed by suppressing excessive ACTH secretion by corticosterone replacement for 7 days (not shown). This suggests that the alterations in adrenal …”

Chromaffin cell function and structure is impaired in corticotropin-releasing hormone receptor type 1-null mice

“…There is a well-established correlation between the production sites for steroidogenesis in adrenocortical cells, as indicated by the number and density of inner mitochondrial membranes and SER, and the biochemical activity of these cells. 27,28 Likewise, the increase in liposomes, the storage organelles for cholesterol, reflect reduced steroid biosynthesis and a hypofunctional adrenocortical state. 29 Consistent with these assumptions, ACTH injections at a dose sufficient to restore thymus weight induced a strong increase in the number of mitochondria and increased density of their internal membranes while the number of liposomes were markedly reduced.…”