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In many types of cells and tissues, the nuclear receptor corepressor 1 (Ncor1) is known as a main corepressor that interacts with thyroid hormone receptors (i.e., TRα, TRβ1, and TRβ2). In the absence of thyroid hormone (T3), NCOR1 is recruited by TRs to inhibit gene transcription. In the liver, the deletion of Ncor1 increases hepatic triglyceride levels. However, the detailed mechanism of how NCOR1 is involved in thyroid hormone signaling in different types of tissues is not fully understood. Our previous study showed that TRβ1 is expressed in the adrenal gland inner cortex and T3 treatment leads to the hypertrophy of this area. To determine the role of NCOR1 in the regulation of thyroid hormone signaling in adrenocortical cells, we generated the mice with a conditional deletion of Ncor1 in the adrenal cortex by crossing the Ncor1 floxed mice with the steroidogenic factor 1 (SF1) Cre mice. The RNA-seq data showed that only 76 genes were differentially expressed in adrenal glands due to the deletion of Ncor1 in adrenocortical cells. Gene ontology (GO) analysis revealed that 'cholesterol synthesis’ was the top GO term associated with these 76 genes. Interestingly, 24-dehydrocholesterol reductase (Dhcr24), the key enzyme for cholesterol synthesis, was upregulated in knockout mice adrenal glands in both sexes. This phenotype fits the results in our previous studies that (1) Dhcr24 is significantly increased under T3 treatment in wild-type mice adrenal glands and (2) the DHCR24-expressing zone in the inner cortex is the primary responsive adrenal cortical layer under T3 treatment which leads to increased lipid accumulation in this area. To further study how DHCR24 is involved in this T3-induced lipid accumulation in the adrenal gland inner cortex, we generated Dhcr24 conditional knockout mice. We found that the T3-induced lipid accumulation in the adrenal gland inner cortex was sharply decreased in the Dhcr24;Sf1-Cre mice. In summary, with the Ncor1 conditional knockout mice, we found that the regulation of the cholesterol synthesis through DHCR24 is the primary function of NCOR1 in the adrenal gland inner cortex; by using the Dhcr24 conditional knockout mice, we further confirmed that the T3-induced lipid accumulation in the adrenal inner cortex can be blocked by the deletion of DHCR24. This study used genetic mouse models to decipher the connection between nuclear receptor corepressor Ncor1, the cholesterol synthesis enzyme Dhcr24, and how they control de novo cholesterol synthesis in the adrenal gland inner cortex. Presentation: Monday, June 13, 2022 11:00 a.m. - 11:15 a.m.

The gender bias in adrenal diseases has been noticed for a long time. Mouse studies have shown that the adrenal gland is sexually dimorphic at different levels, such as transcriptome, histology, and cell renewal. However, the mechanism behind this sexual dimorphism is not fully understood. Here, we used RNA-seq to demonstrate how male and female adrenals respond differently to the same external cue, the thyroid hormone (T3) treatment, which directly elicits its function on the adrenal inner cortex by changing the cell fate of this population. Through the comparison of the adrenal gland transcriptomes from males and females with T3 or saline treatment, we found that more genes in female adrenals were responsive to the T3 treatment, whereas the fold change of the gene expressions was greater in male adrenals. Statistical analysis identified 104 sexually dimorphic T3-responsive genes. Immunostaining results showed that many of these genes were expressed in the adrenal gland inner cortex, which contains a unique cell population called X-zone (20-alpha-HSD positive). Previous studies showed that T3 treatment leads to the expansion of the 20αHSD-positive zone both in males and in females. Here we found that the top sexually dimorphic T3-responsive gene was expressed in the adrenal inner cortex partially colocalized with X-zone. Under T3 treatment, this unique cell population that surrounds the 20-alpha-HSD positive X-zone became obvious only in females but not in males. Our findings not only identified several novel marker genes for the adrenal inner cortex but also highlighted the sex-specific response of thyroid hormone action in the mouse adrenal gland.

It is well known that thyroid hormone plays a key role in amphibian metamorphosis and mammalian tissue remodeling. We and others have reported that treatment with thyroid hormone will prevent or postpone the regression of the adrenal inner cortex (X-zone) and leads to X-zone hypertrophy in mice. The expression of thyroid hormone receptor beta 1 (TRβ1) in the adrenal inner cortex indicates that thyroid hormone could elicit its function directly on this cell population. To support this idea, we examined the expression and the function of major thyroid hormone transporters Mct8, Mct10, and Oatp1c1 in mouse adrenal glands. RNA-seq data showed that the expression levels of Mct10 and Oatp1c1 are relatively low in the adrenal gland (with RPKM less than 5 and 1, respectively) whereas Mct8 is the most abundant transporter (with RPKM around 20). Quantitative RT-PCR showed that Mct8 in the adrenal gland has an expression profile similar to X-zone marker genes and TRβ1 throughout developmental stages. LacZ staining showed similarities between Mct8 and TRβ1 expression, with both specifically expressed in the most inner cortex of the adrenal gland next to the medulla. However, by using thyroid hormone (T3) treatment, we found that the T3-mediated effect in the adrenal gland was not fully blocked in Mct8 knock-out mice. The expression of thyroid hormone transporter Mct8 in the adrenal inner cortex supports our claim that transporters mediate the direct action of thyroid hormone in the adrenal inner cortex. The blunted response to thyroid hormone in Mct8 knockout mice suggests that Mct8 is responsible for the thyroid hormone action in the adrenal gland. However, the deletion of Mct8 does not completely block thyroid hormones effect in the adrenal gland. Our finding suggests other thyroid hormone transporter(s) in the adrenal gland are also responsible for thyroid hormone signaling in the adrenal gland.

The fluorescent dye Lucifer Yellow (LY) is a well-known and widely-used marker for fluid-phase endocytosis. In this paper, both light and electron microscopy revealed that LY was internalized into transition zone cells of the inner cortex of intact maize root apices. The internalized LY was localized within tubulo-vesicular compartments invaginating from the plasma membrane at actomyosin-enriched pit-fields and individual plasmodesmata, as well as within adjacent small peripheral vacuoles. The internalization of LY was blocked by pretreating the roots with the F-actin depolymerizing drug latrunculin B, but not with the F-actin stabilizer jasplakinolide. F-actin enriched plasmodesmata and pit-fields of the inner cortex also contain abundant plant-specific unconventional class VIII myosin(s). In addition, 2,3 butanedione monoxime, a general inhibitor of myosin ATPases, partially inhibited the uptake of LY into cells of the inner cortex. Conversely, loss of microtubules did not inhibit fluid-phase endocytosis of LY into these cells. In conclusion, specialized actin- and myosin VIII-enriched membrane domains perform a tissue-specific form of fluid-phase endocytosis in maize root apices. The possible physiological relevance of this process is discussed.

Regulation of nodule permeability in response to short-term changes in environmental and physiological conditions is thought to occur by occlusion of intercellular spacesin the nodule inner cortex. To test this hypothesis, the permeability of legume nodules was altered by adapting them to either 20 or 80% O 2 over a 2.5-h period. The nodules were then rapidly frozen, cryo-planed and examined under cryo-scanning electron microscopy for differences in the number, area or shape factor of intercellular spaces

A pea cDNA clone homologous to the soybean early nodulin clone pGmENOD2 that most probably encodes a cell wall protein was isolated. The derived amino acid sequence of the pea ENOD2 protein shows that it contains the same repeating pentapeptides, ProProHisGluLys and ProProGluTyrGln, as the soybean ENOD2 protein. By in situ hybridization the expression of the ENOD2 gene was shown to occur only in the inner cortex of the indeterminate pea nodule. The transcription of the pea ENOD2 gene starts when the inner cortical cells develop from the nodule meristem. In the determinate soybean nodule the ENOD2 gene is expressed in the inner cortex as well as in cells surrounding the vascular bundle that connects the nodule with the root central cylinder. The term 'nodule inner cortex' is misleading, as there is no direct homology with the root inner cortex. Therefore, we propose to consider this tissue as nodule parenchyma. A possible role of ENOD2 in a major function of the nodule parenchyma, namely creating an oxygen barrier for the central tissue with the Rhizobium containing cells, is discussed.

The inner cortex of two yam cultivars – Obiaoturugo (Dioscorea rotundata Poir) and Um680 (D.alata L.) were extruded, leaving a 1cm wall with the periderm. The two sett types (hollow and intact) in both cultivars, gave similar fresh tuber yields. Growth attributes of the yam vines were also fairly similar. It is suggested that the 1cm outer layer of ware tubers, usually thrown away, can be re-cycled the following cropping season to raise ware tubers. [Niger Agric. J. 34 (2003): 68-73]

The inner cortex of two yam cultivars – Obiaoturugo (Dioscorea rotundata Poir) and Um680 (D.alata L.) were extruded, leaving a 1cm wall with the periderm. The two sett types (hollow and intact) in both cultivars, gave similar fresh tuber yields. Growth attributes of the yam vines were also fairly similar. It is suggested that the 1cm outer layer of ware tubers, usually thrown away, can be re-cycled the following cropping season to raise ware tubers. [Niger Agric. J. 34 (2003): 68-73]

After a 2 h exposure of intact soybean nodules to high concentrations of NaCl (100mol m−3) or oxygen (8OkPa O2), morphometric computations carried out using an image analysis technique on semi-thin sections showed that both treatments induced a decrease in the area of the inner-cortex cells, which were then characterized by a tangential elongation. In contrast, no significant change in area occurred in the middle-cortex cells although their elongation decreased. Electron microscopic observations showed that in the inner-cortex cells changes included the presence of wall infoldings, an enlarged periplasmic space and a lobate nucleus whose chromatin distribution differed from that of the control. Structural changes also occurred in the endoplasmic reticulum, microbodies, mitochondria and plastids. From several of these changes, which are similar to those noted in osmocontractil cells in response to external stimuli, it can be hypothesized that the inner cortex may provide a potential mechanism for the control of oxygen diffusion through the nodules.

Renal hemodynamic effects of the angiotensin-converting enzyme inhibitor enalapril diacid (30 micrograms/kg, i.v.; n = 8) were examined using laser-Doppler flowmetry in anesthetized dogs. Two laser-Doppler flowmetry probes were applied simultaneously to measure the renal blood flow of the outer and inner cortex. Changes in cortical renal blood flow, obtained by the laser-Doppler flowmetry method, were intimately related to those in total renal blood flow measured with the electromagnetic flow probe during occlusion of the abdominal aorta or after administration of angiotensin II, norepinephrine, acetylcholine or dopamine. Enalapril diacid produced a significant increase in total renal blood flow, despite moderate hypotension. The blood flow of the inner cortex significantly increased by 21% following enalapril diacid, while that of the outer cortex did not. These data indicate that there may be a regional difference in the intrarenal vasodilating effect of enalapril diacid. These results also demonstrate that the laser-Doppler flowmetry method is suitable for the continuous measurement of directional changes in both outer and inner cortical blood flows.

A pea cDNA clone homologous to the soybean early nodulin clone pGmENOD2 that most probably encodes a cell wall protein was isolated. The derived amino acid sequence of the pea ENOD2 protein shows that it contains the same repeating pentapeptides, ProProHisGluLys and ProProGluTyrGln, as the soybean ENOD2 protein. By in situ hybridization the expression of the ENOD2 gene was shown to occur only in the inner cortex of the indeterminate pea nodule. The transcription of the pea ENOD2 gene starts when the inner cortical cells develop from the nodule meristem. In the determinate soybean nodule the ENOD2 gene is expressed in the inner cortex as well as in cells surrounding the vascular bundle that connects the nodule with the root central cylinder. The term 'nodule inner cortex' is misleading, as there is no direct homology with the root inner cortex. Therefore, we propose to consider this tissue as nodule parenchyma. A possible role of ENOD2 in a major function of the nodule parenchyma, namely creating an oxygen barrier for the central tissue with the Rhizobium containing cells, is discussed.

A pea cDNA clone homologous to the soybean early nodulin clone pGmENOD2 that most probably encodes a cell wall protein was isolated. The derived amino acid sequence of the pea ENOD2 protein shows that it contains the same repeating pentapeptides, ProProHisGluLys and ProProGluTyrGln, as the soybean ENOD2 protein. By in situ hybridization the expression of the ENOD2 gene was shown to occur only in the inner cortex of the indeterminate pea nodule. The transcription of the pea ENOD2 gene starts when the inner cortical cells develop from the nodule meristem. In the determinate soybean nodule the ENOD2 gene is expressed in the inner cortex as well as in cells surrounding the vascular bundle that connects the nodule with the root central cylinder. The term 'nodule inner cortex' is misleading, as there is no direct homology with the root inner cortex. Therefore, we propose to consider this tissue as nodule parenchyma. A possible role of ENOD2 in a major function of the nodule parenchyma, namely creating an oxygen barrier for the central tissue with the Rhizobium containing cells, is discussed.

The morphological change of the cell surface in the inner zone of the adrenal cortex was studied in intact, hypophysectomized, and ACTH-treated hypophysectomized rats, using freeze-fracture replicas. In both intact and hypophysectomized ACTH-treated animals, the P fracture face of the plasma membranes of the cortical cells facing capillaries shows groups of characteristic finger-shaped microvilli, which arise horizontally from the edges of a small cavity on the cell surface to form various configurations ranging from incompletely organized, flower budlike to complicated, arboraceous ones. In the non-treated hypophysectomized animals, however, the microvilli in such groups decrease in number and shorten in length but increase in width, looking like a blade of a prickly-pear cactus or an irregular-shaped plate. On the other hand, presumptive exocytotic and endocytotic specializations of intra-membranous particles were observed on the lateral plasma membrane, but they appeared only rarely and in both normal and experimental animals.

Summary Regional distribution of angiotensin converting enzyme(ACE) in the rat kidney was studied. The ACE activities in the inner cortex and outer medulla were about 10 and 5 times those in the outer cortex, respectively. The activity in the inner medulla or papilla was much the same as that in the outer cortex. Immunofluorescence was greatest in the proximal tubules in the inner cortex, while the outer medulla and the inner medulla or papilla showed a weak fluorescence. The brush border membranes isolated from the inner cortex also possessed about 10 times the ACE activity seen in the outer cortex. The results indicate that the major source of renal ACE is not the proximal convoluted tubules in the outer cortex, but rather the brush border membranes of proximal tubules in the inner cortex. The contribution of ACE in the inner cortex would therefore be predominant.

The rat kidney was separated into the outer cortex, inner cortex, outer medulla and inner medulla or papilla, and the distribution of angiotensin-converting enzyme (ACE) in response to consecutive administrations of captopril was studied. In normal animals, the ACE activity in the inner cortex and outer medulla was about 10 and 3 times higher than in the outer cortex, respectively, and the activity in the inner medulla was much the same as that in the outer cortex. Captopril was given in doses of 30 and 100 mg/kg/day for 7 days, and the renal ACE activity on the 8th day was examined. Since it was assumed that the ACE activity might be lower than the full activity when the tissue contained captopril, diamide, a sulfhydryl oxidant, was used to eliminate the effect of any captopril remaining in the tissue extracts. However, this compound at concentrations over 1 mM enhanced the activity of ACE itself to about twice the value when assayed without diamide. Thus, oxidation with sufficient concentrations of diamide resulted in an enhancement of a maximal activity of ACE. When all samples were pretreated with 10 mM diamide and the ACE activity determined, captopril caused a dose-related increase in the ACE activity, but only in the inner cortex. We conclude that ACE locates predominantly in the inner cortex of the rat kidney and it is this area which has an altered ACE activity in response to captopril.