Non‐invasive, quantitative assessment of the anatomical phenotype of corticotropin‐releasing factor‐overexpressing mice by MRI

Abstract

High resolution magnetic resonance imaging (MRI) was applied to quantify alterations in thymus and adrenal volumes, as well as body fat in genetically engineered corticotropin-releasing factor (CRF)-overexpressing mice. When compared to the organs in age-matched wild-type animals, the adrenals in CRF-overexpressing male mice were significantly enlarged and the thymus volume in females was significantly smaller. The fat content was significantly larger in CRF-overexpressing mice. The anatomical alterations observed in the MRI studies were in perfect line with post-mortem data (weights of organs). Furthermore, the observed interstrain differences are in agreement with recently published data on (i) the effect of continuous, intraventricular infusion of CRF in rats and (ii) the presence of atrophic adrenals in CRF-knockout mice. The present studies demonstrate that MRI can provide reliable measures of relatively small structures such as the adrenal glands and the thymus in mice. This makes MRI an attractive, non-terminal tool to monitor in laboratory animals, including transgenic mice, the consequence of continuous stress on relevant organs.

Corticotropin-releasing factor overexpression in mice abrogates sex differences in body weight, visceral fat, and food intake response to a fast and alters levels of feeding regulatory hormones

“…Likewise, under condition of CRF-OE expression primarily in specific brain nuclei [1, 2], the adrenal glands’ weight was significantly higher in CRF-OE than in WT mice and there was a sex difference (females > males) in both genotypes consistent with previous reports [3, 12, 31]. This enlargement in CRF-OE mice is related to the hypertrophy of the adrenal cortex, a zone known to be involved in the corticosteroid synthesis and secretion, while the adrenal medulla is not altered [3, 12, 31]. Consistent with these previous histological findings [3, 12, 31], there is a high correlation between the adrenal gland weights and levels of plasma corticosterone in male and female CRF-OE mice and WT littermates.…”

“…This enlargement in CRF-OE mice is related to the hypertrophy of the adrenal cortex, a zone known to be involved in the corticosteroid synthesis and secretion, while the adrenal medulla is not altered [3, 12, 31]. Consistent with these previous histological findings [3, 12, 31], there is a high correlation between the adrenal gland weights and levels of plasma corticosterone in male and female CRF-OE mice and WT littermates. Although there was no significant sex difference in corticosterone levels, the correlation indicates to some extent that enlarged glands lead to high corticosterone production.…”

“…Whether this reflects a potential influence of gonadal steroid hormones interaction with CRF signaling in the brain needs to be further investigated. In addition, the higher adrenal gland volume [3, 12, 31] and blood glucose levels in female than male CRF-OE mice may be consistent with the elevated locus coeruleus neuronal activity selectively occurring in female CRF-OE mice compared to males driving sympathetic outflow [12]. …”

“…Other studies showed that the weights of perirenal and inguinal fat and the total body fat content were also increased when assessed either in male or female CRF transgenic mice [22, 31]. The hypertrophy of abdominal adipose tissue is known to occur with glucocorticoid excess [32–34].…”

Fat-Storing Multilocular Cells Expressing CCR5 Increase in the Thymus with Advancing Age: Potential Role for CCR5 Ligands on the Differentiation and Migration of Preadipocytes

“…While these data do not directly demonstrate the ability of chemokine ligands to facilitate primary mesenchymal cell differentiation to the adipocyte lineage, these experiments support the idea that chemokines may be possibly acting as chemoattractants for adipogenic mesenchymal and/or fat-storing cells, facilitating their immigration and possibly their subsequent differentiation within the aging thymic microenvironment. Although additional work will be needed to establish a role for adipogenic cells in the thymus, several groups have shown thymic atrophy in transgenic mice harboring defects in adipocyte physiology, such as ob/ob (leptin), db/db (leptin receptor) and corticotropin-releasing factor overexpressing mice 40, 41. In this context, reducing proadipogenic signaling in caloric restriction model leads to a reduction in age-associated thymic involution 42.…”