Disease relevance of Zona Reticularis

• These findings of basal and ACTH-stimulated hypersecretion of delta 5-androgens in patients with postaldolescent acne are consistent with an increased volume of androgen-secreting tissue, rather than hypersensitivity of the adrenal zona reticularis to ACTH [1].
• However, the cause of adrenal androgen hypersecretion is not yet fully understood but it may include endogenous hypersecretion of the zona reticularis of unclear cause, hypersecretion of cortical-androgen-stimulating hormone (CASH), stress, hyperprolactinemia, adrenal enzymatic defects etc [2].
• In the present study, the width of the zona reticularis was studied single blind in multiple sections of the adrenals of 42 victims of sudden death 4 months to 93 years of age to discern a possible correlation between zona reticularis width and the declining adrenal androgen levels and excretion typical of aging [3].
• Similarly, low birthweight and subsequent rapid postnatal weight gain are associated with increased androgen secretion from the adrenal zona reticularis and this may contribute to disorders of hyperandrogenism and hyperinsulinemia before and after puberty [4].
• On the contrary, prolonged prolactin treatment induced a conspicuous hypertrophy of zona reticularis cells, as well as a notable rise in the plasma concentration of testosterone, which cannot be due to gonad stimulation by prolactin since orchiectomized rats were employed [5].

High impact information on Zona Reticularis

• These tissues include ovarian steroidogenic theca cells and lutein cells of the corpus luteum, testosterone-producing Leydig cells of the testis, steroidogenic cells confined to the zona reticularis of the adrenal cortex, and progesterone-producing cells of the placenta [6].
• SR-BI was localized by immunofluorescence to the surfaces of steroidogenic cells in the zona fasciculata and zona reticularis of the adrenal gland and to the corpus luteal cells of the ovary [7].
• In vitro alkaline phosphatase treatment of the PBP abolished pregnenolone-binding activity and caused an alteration in the charge-isoform pattern for PBP in the zona reticularis, where pregnenolone binding is high, to resemble the pattern found for the zona fasciculata, where pregnenolone binding is low [8].
• Additionally, the pregnenolone-binding activity was approximately 10-fold greater in the zona reticularis [8].
• In contrast, the production of dehydroepiandrosterone (DHEA) and DHEA sulfate in the adrenal reticularis is inversely correlated with the expression of HSD3B2 [9].

Biological context of Zona Reticularis

• Adrenarche results from development of a 3beta-hydroxysteroid dehydrogenase-deficient adrenal reticularis [10].
• These observations suggest that differential regulation of microsomal functions for steroid hydroxylation and drug metabolism occurs largely in the zona reticularis [11].
• Cell proliferation index (Ki-67) in the outer, subcapsular, zona glomerulosa was significantly higher than in zona fasciculata of all groups and in zona reticularis or fetal zone [12].
• We report here that the adrenal morphology of reproductively inhibited deermice raised within laboratory populations is different from patterns seen with normal puberty; namely in the area, histology, and apparent activity of the weak androgen-secreting zona reticularis [13].
• Incubation of microsomes from the zona reticularis (ZR) of the guinea pig adrenal cortex with CCl4 plus NADPH caused initiation of lipid peroxidation, covalent binding of CCl4-derived radioactivity to protein, and degradation of cytochrome(s) P450 [14].

Anatomical context of Zona Reticularis

• D4 receptors were mainly localized in the zona glomerulosa and, to a lesser extent, in the zona reticularis [15].
• In the adrenal cortex, cells of the zona reticularis and zona fasciculata but not the zona glomerulosa were positive, whereas in the adrenal medulla viral nucleic acid was predominantly localized to adrenalin-secreting cells [16].
• With such a mechanism, it is difficult to conceive how high amounts of DHEA may be produced in some cells or tissues, such as the testis and cells from the adrenal reticularis, while in other tissues such as the fasciculata zone, high levels of 17alpha-OHPreg are synthesized [17].
• Cholesterol side-chain cleavage activity in mitochondria isolated from the outer and inner zones of the guinea pig adrenal cortex was evaluated in order to clarify the role of the zona reticularis in steroidogenesis [18].
• RESULTS: Tumour growth factor-beta receptor-1 (TGFbeta-R1) and CYP-11 were found to be expressed predominantly in the zona fasciculata, whereas human leukocyte antigen (HLA-DR) and CYP-17 were localised to the zona reticularis [19].

Associations of Zona Reticularis with chemical compounds

• In addition to the cytochrome P450 enzymes that are important in steroid biosynthesis, dehydroepiandrosterone sulfotransferase (DST) is likely to be a key regulated enzyme in the formation of sulfated steroids, which are characteristic of the human adrenal cortex, particularly that of the fetus and the adult zona reticularis [20].
• In addition, the relations between ACTH, the classic stimulus of cortisol and adrenal androgens, and these hormones are weakened or abolished, whereas the negative relation between age and zona reticularis function is steeper than that of controls [21].
• A reduced mass of the zona reticularis could be responsible for the diminished production of dehydroepiandrosterone and dehydroepiandrosterone sulfate that occurs during aging [22].
• These findings suggest that as children mature there is a decreased level of 3betaHSD in the adrenal reticularis that may contribute to the increased production of DHEA and DHEAS seen during adrenarche [10].
• It is suggested that the relatively low activity of ACAT may not always be explained by the reduced content of cholesterol in the microsomal fraction of zona reticularis [23].

Gene context of Zona Reticularis

• IL-1 enhances the proliferation of adrenocortical cells, and findings suggest that cytokines may control the apoptotic deletion of senescent zona reticularis cells [24].
• A recent study showed GATA-6 expression in the adrenal reticularis, the source of adrenal androgens [25].
• After sodium restriction, AT1 receptors appeared to be uniformly distributed within an enlarged ZG; furthermore AT1 receptor-positive cells were found to a limited degree in the zona fasciculata and possibly in the zona reticularis, and a greater number of these positive cells appeared in these zones under sodium restriction [26].
• Adrenarche is thought to be governed by a dual control mechanism in which an adrenal androgen secretagogue acts upon a zona reticularis primed by ACTH [27].
• We suggest that the enigma of adrenarche may have an elegant solution, with CRH and ACTH coupled in sequence at the hypothalamic-pituitary level, and in parallel within the zona reticularis, just as they presumably are within the fetal adrenal, which is exposed to CRH of placental origin [27].

Analytical, diagnostic and therapeutic context of Zona Reticularis

• Both orchiectomy and testosterone shortened this phase in cells of the zona fasciculata and zona reticularis [28].
• Immunohistochemistry demonstrated the presence of a cytochrome-P-450-like protein in the adrenal-cortical cells (especially in the zona-reticularis cells) of MC-treated female mice; at the same time, a remarkable increase in the amount of SER in these cells was observed by electron microscopy [29].

References