Ontogeny of the Adrenal Gland in the Spiny Mouse, With Particular Reference to Production of the Steroids Cortisol and Dehydroepiandrosterone

Abstract

Synthesis of the androgen dehydroepiandrosterone (DHEA) by the fetal adrenal gland is important for placental estrogen production and may also be important for modulating the effects of glucocorticoids on the developing brain. The presence of cortisol in spiny mouse (Acomys cahirinus) blood led us to determine whether the adrenal gland of this precocial rodent also synthesized DHEA. Cytochrome P450 enzyme 17α-hydroxylase/17,20-lyase (P450c17), cytochrome-b5 (Cytb5), and 3β-hydroxysteroid dehydrogenase (3βHSD) were detected in the adrenal gland from 30 days gestation (term = 39 days), and DHEA, cortisol, and aldosterone were detected in fetal plasma from this time. Plasma DHEA concentrations increased 4-fold, whereas cortisol concentrations decreased from day 30 of gestation until the day of birth. Explant culture of fetal adrenal tissue showed that DHEA was produced from exogenous pregnenolone, and thus, the DHEA in the fetal circulation is likely to be of fetal origin. Clear zonation of the fetal adrenal cortex was evident by 38 days gestation when expression of Cytb5 was present throughout the cortex, and coexpression of P450c17 and Cytb5 occurred in the zona reticularis and fasciculata. 3βHSD was expressed in the cortex from at least 30 days gestation and decreased as term approached, consistent with the fall of cortisol in late gestation in this species. These results show that the spiny mouse adrenal gland, like that of the human fetus, can synthesize and secrete DHEA from at least 30 days (relative gestation length, 30 days of a 39-day gestation, 0.76) of gestation, and DHEA may have important roles in placental biosynthesis of estrogens and in modulating the actions of glucocorticoids in the developing brain in this species.

Adrenal glands of Spix's yellow-toothed cavy (Galea spixii, Wagler, 1831): morphological and morphometric aspects

“…In rats and Balb/c mice, the cytochrome P450c17 is absent in adrenal and therefore the authors suggest that this organ does not contribute to production of androgens (van-Weerden et al, 1992). However, in C. porcellus, the cytochrome P450c17 enzyme is predominantly distributed in the fasciculate zone, but is also found in lower quantities in the reticular zone (Shinzawa et al, 1988), as also found in Spiny mouse (Quinn et al, 2013). In the absence of P450c17 in the glomerular zone C21-deoxy-steroids are produced, leading to mineralocorticoids aldosterone.…”

“…Each part of adrenal gland has different cell types: cells producing sexual steroid hormones, glucocorticoids and mineralocorticoids are present in the cortex, and chromaffin cells, which are producers of catecholamine and neuropeptides are present in medullar region (Hîncu et al, 2006;Kempná and Flück, 2008;Chang et al, 2011;Parker et al, 2011;Quinn et al, 2013;Qiu et al, 2013).…”

“…Some studies have focused on the ultrastructure and morphology of the different cell types present in each layer of the adrenal cortex and medulla during intrauterine development and the immunolocalization of steroidogenic enzymes, especially that responsible for androgens production, as cytochrome P450c17 in species of wild mammals (Quinn et al, 2013). In this sense, the authors have found different sites of androgen production in adrenal glands of different species, as mice (Chang et al, 2011), Rattus norvegicus (van-Weerden et al, 1992;Pignatelli et al, 1998), Balb/c mouse (van-Weerden et al, 1992) and spiny mice (Quinn et al, 2013).…”

“…In this sense, the authors have found different sites of androgen production in adrenal glands of different species, as mice (Chang et al, 2011), Rattus norvegicus (van-Weerden et al, 1992;Pignatelli et al, 1998), Balb/c mouse (van-Weerden et al, 1992) and spiny mice (Quinn et al, 2013). Cytochrome P450c17 catalyses two distinct reactions: the 17α-hydroxylation of C 21 (molecules with 21 atoms of carbon) steroids and the conversion of the 17α-hydroxylated C 21 steroids to C 19 (molecules with 19 atoms of carbon) steroids.…”

PKA signaling drives reticularis differentiation and sexually dimorphic adrenal cortex renewal

“…Because rats and mice lack postnatal expression of CYP17 in the adrenal, they have long been considered as nonrelevant experimental models to study adrenarche. However, the spiny mouse has been shown to express CYP17 and to produce adrenal-derived androgens from an individualized zR (47)(48)(49). This provides cues for possible usefulness of rodent models to explore underpinnings of adrenarche.…”