Zona Reticularis

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Alan J Conley - One of the best experts on this subject based on the ideXlab platform.

  • 1 Morphological Adrenarche in Rhesus Macaques: Development of the Zona Reticularis is Concurrent with Fetal Zone Regression in the Early Neonatal Period
    2016
    Co-Authors: Ann D. Nguyen, Samantha Mapes, Jo C Corbin, Alan J Conley
    Abstract:

    Human adrenarche is associated with the establishment of a functional Zona Reticularis (ZR) and increasing secretion of dehydroepiandrosterone (DHEA) in sulphated form (DS). Like most non-human primates, rhesus macaques are not believed to undergo adrenarche, though they clearly establish a functional ZR after birth. However, the origins of the rhesus ZR are not well defined. Therefore, we investigated the Zonal development, steroidogenic enzyme expression and morphology of rhesus adrenals from 20 1 day to 14 months of age. Immuno-histochemistry was conducted to determine expression profiles of the steroidogenic enzymes 17α-hydroxylase/17,20-lyase cytochrome P450 (P450c17), 21-hydroxylase cytochrome P450 (P450c21), 3β-hydroxysteroid dehydrogenase/∆5-4 isomerase (3β-HSD), the redox partner NADPH-cytochrome P450 oxidoreductase (CPR), as well as the accessory protein cytochrome b5 (b5), a marker of the primate ZR. The rhesus ZR is mature by 3 months of age based on differentiation of the innermost zone which lacks 3β-HSD, but exhibits increased b5 expression during this period. Further, the ZR develops in neonates from a previously described dense band of cells which we show expresses b5, P450c17, CPR, and P450c21 throughout maturation. The fetal zone (FZ) is distinguished from the ZR by its lack of 30 P450c21, and ZR development proceeded as the FZ regressed with two important implications: neither FZ regression nor ZR maturation can be monitored independently by circulating adrenal androgens, and these events must be induced by different factors in rhesus, and likely humans. Collectively, these data demonstrate that ZR development begins before birth in the rhesus, proceeding concomitant with FZ regression post

  • Plasticity of the Zona Reticularis in the adult marmoset adrenal cortex: voyages of discovery in the New World.
    The Journal of endocrinology, 2009
    Co-Authors: J. Christina Pattison, Alan J Conley, David H. Abbott, Wendy Saltzman, Ian M. Bird
    Abstract:

    Adrenarche in humans occurs at the age of 5–7 years, yet the process by which dehydroepiandrosterone (DHEA) biosynthesis in the adrenal Zona Reticularis (ZR) increases so dramatically remains as a matter of debate. One suggestion is that increased DHEA production by P450c17 (CYP17A1 as listed in HUGO Database) in the ZR results from a coincident fall in the expression of HSD3B, which would otherwise compete for pregnenolone substrate. Nonetheless, studies of human and rhesus adrenal show that cytochrome b5 (CYTB5) expression increases in the ZR with DHEA biosynthesis, and cloned human and rhesus P450c17 show selective increases in 17,20-lyase activity in the presence of CYTB5. The marmoset, a New World primate, expresses a fetal zone during development which regresses after birth. Adult males, however, do not develop an obvious functional ZR, while females develop a ZR in a manner that depends on their social/gonadal status. In all social and physiologic states, changes in marmoset ZR function relate directly to changes in the expression of CYTB5. Recent cloning and expression of marmoset P450c17 also show that while amino acid sequence homology is in the order ofw85% of that found in human and rhesus sequences, and basal lyase activity is low compared with rhesus, all previously described amino acids critical to human 17,20-lyase activity are completely conserved. Furthermore, the 17,20-lyase activity of the marmoset P450c17 clone is dramatically increased by addition of CYTB5. We propose that these combined data from the marmoset model provide further compelling evidence that the control of ZR CYTB5 expression is a key determinant of ZR function.

  • Morphological adrenarche in rhesus macaques: development of the Zona Reticularis is concurrent with fetal zone regression in the early neonatal period
    Journal of Endocrinology, 2008
    Co-Authors: Ann D. Nguyen, Samantha Mapes, C. Jo Corbin, Alan J Conley
    Abstract:

    Human adrenarche is associated with the establishment of a functional Zona Reticularis (ZR) and increasing secretion of dehydroepiandrosterone (DHEA) in sulfated form (DS). Like most non-human primates, rhesus macaques are not believed to undergo adrenarche, though they clearly establish a functional ZR after birth. However, the origins of the rhesus ZR are not well defined. Therefore, we investigated the Zonal development, steroidogenic enzyme expression and morphology of rhesus adrenals from 1 day to 14 months of age. Immunohistochemistry was conducted to determine expression profiles of the steroidogenic enzymes 17alpha-hydroxylase/17,20-lyase cytochrome P450, family 17, subfamily A, polypeptide 1 (CYP17A1), cytochrome P450, family 21, subfamily A, polypeptide 2 (CYP21A2), hydroxy-Delta-5-steroid dehydrogenase, 3beta- and steroid Delta-isomerase 2 (HSD3B2), the redox partner NADPH-cytochrome P450 oxidoreductase (CPR), as well as the accessory protein cytochrome b5 (b5), a marker of the primate ZR. The rhesus ZR is mature by 3 months of age based on differentiation of the innermost zone that lacks HSD3B2, but exhibits increased b5 expression during this period. Further, the ZR develops in neonates from a previously described dense band of cells which we show expresses b5, CYP17A1, CPR, and CYP21A2 throughout maturation. The fetal zone (FZ) is distinguished from the ZR by its lack of CYP21A2, and ZR development proceeded as the FZ regressed with two important implications: neither FZ regression nor ZR maturation can be monitored independently by circulating adrenal androgens, and these events must be induced by different factors in rhesus, and likely humans. Collectively these data demonstrate that ZR development begins before birth in the rhesus, proceeding concomitantly with FZ regression post-natally, suggesting that rhesus experiences morphological adrenarche during the first three months of life.

  • Male marmoset monkeys express an adrenal fetal zone at birth, but not a Zona Reticularis in adulthood.
    Endocrinology, 2004
    Co-Authors: J. Christina Pattison, Ann D. Nguyen, Alan J Conley, David H. Abbott, Wendy Saltzman, Gary L. Henderson, Hongwu Jing, Christopher R. Pryce, Amy J. Allen, Ian M. Bird
    Abstract:

    Neonatal human males produce high levels of dehydroepiandrosterone (DHEA) and its sulfo-conjugated form (DS) that decline within a few months of birth, due to regression of the adrenal fetal zone (FZ). Adult male humans and rhesus monkeys produce C19 steroids in abundance from the adrenal Zona Reticularis (ZR). Male marmoset monkeys produce DS at birth, but unlike humans and rhesus monkeys, do not produce comparable amounts of DHEA and DS in adulthood. To determine whether male marmosets express a functional ZR in adulthood, we examined adult and neonatal male marmosets for the presence of a ZR and FZ, respectively. Exogenous ACTH failed to stimulate DHEA or DS in adults, and dexamethasone treatment failed to suppress DHEA and DS, although cortisol levels changed as expected. In steroidogenic tissues, the key proteins necessary to synthesize C19 steroids from pregnenolone are P450c17, 3beta-hydroxysteroid dehydrogenase (3beta-HSD), nicotinamide adenine dinucleotide phosphate (reduced) oxido-reductase cytochrome P450 (reductase), and cytochromeb5 (cytb5). Adult adrenal cross sections showed P450c17 and reductase protein expression throughout the cortex but showed no expected decrease in 3beta-HSD and increase in cytb5 in the innermost region. Western analysis confirmed these data, demonstrating comparable P450c17 expression to rhesus monkeys, but not cytb5. HPLC analysis revealed similar 17alpha-hydroxylase action on pregnenolone for adult marmoset and rhesus adrenal microsomes but greatly diminished 17,20-lyase activity in marmosets. Neonatal marmoset adrenals exhibited staining indicative of a putative FZ (with P450c17, reduced 3beta-HSD and increased cytb5). We conclude that neonatal marmosets exhibit a C19 steroid-secreting FZ similar to humans, but adult males fail to acquire a functional ZR.

  • The Primate Adrenal Zona Reticularis is Defined by Expression of Cytochrome b5, 17α-hydroxylase/17,20-lyase Cytochrome P450 (P450c17) and NADPH-Cytochrome P450 Reductase (reductase) but not 3β-Hydroxysteroid Dehydrogenase/Δ5-4 Isomerase (3β-HSD)
    The Journal of clinical endocrinology and metabolism, 1999
    Co-Authors: Samantha Mapes, C. Jo Corbin, Alice F. Tarantal, Alan J Conley
    Abstract:

    Biochemical studies suggest that 17,20-lyase activity, and thus efficient synthesis of androgens by human P450c17, requires both reductase and the accessory protein cytochrome b5. Since the human and primate Zona Reticularis (ZR) secrete androgens, the expression of these proteins, and of 3β-HSD, was investigated by immunocytochemistry in the adrenal cortex of the mature rhesus macaque. Cytochrome b5 expression was restricted to the cells of the ZR which appeared deficient in 3β-HSD. However, both P450c17 and reductase were evident throughout the Zona fasciculata. These data provide essential evidence in support of a functional role for cytochrome b5 in the regional control of 17α-hydroxylase and 17,20-lyase activities of P450c17 and thereby adrenal C19 steroid secretion by the primate adrenal gland.

William E. Rainey - One of the best experts on this subject based on the ideXlab platform.

  • *Correspondence and reprint requests addressed to:
    2016
    Co-Authors: Xiao Gang Hui, William E. Rainey, Yasuhiro Nakamura, Jun-ichi Akahira, Takashi Suzuki, Masaki Nio, Hironobu Sasano
    Abstract:

    Development of the human adrenal Zona Reticularis

  • transcriptome profiling reveals differentially expressed transcripts between the human adrenal Zona fasciculata and Zona Reticularis
    The Journal of Clinical Endocrinology and Metabolism, 2014
    Co-Authors: Juilee Rege, Todd D Merchen, Hironobu Sasano, Yasuhiro Nakamura, Tao Wang, William E. Rainey
    Abstract:

    Context: The human adrenal Zona fasciculata (ZF) and Zona Reticularis (ZR) are responsible for the production of cortisol and 19-carbon steroids (often called adrenal androgens), respectively. However, the gene profiles and exact molecular mechanisms leading to the functional phenotype of the ZF and ZR are still not clearly defined. In the present study, we identified the transcripts that are differentially expressed in the ZF and ZR. Objective: The objective of the study was to compare the transcriptome profiles of ZF and ZR. Design and Methods: ZF and ZR were microdissected from 10 human adrenals. Total RNA was extracted from 10 ZF/ZR pairs and hybridized to Illumina microarray chips. The 10 most differentially expressed transcripts were studied with quantitative RT-PCR (qPCR). Immunohistochemistry was also performed on four zone-specific genes. Results: Microarray results demonstrated that only 347 transcripts of the 47 231 were significantly different by 2-fold or greater in the ZF and ZR. ZF had 195 ...

  • Clinical, Biochemical, and Molecular Characterization of Macronodular Adrenocortical Hyperplasia of the Zona Reticularis: A New Syndrome
    Endocrinology, 2010
    Co-Authors: Hans K. Ghayee, Juilee Rege, William E. Rainey, Lori M Watumull, Fiemu E. Nwariaku, Kelley S. Carrick, Walter L. Miller, Richard J. Auchus
    Abstract:

    Context: Macronodular adrenocortical hyperplasia classically presents with progressive hypercortisolemia and Cushing syndrome. We describe a 29-year-old man with massive macronodular adrenocortical hyperplasia without hypercortisolemia but rather markedly elevated and nonsuppressible production of dehydroepiandrosterone (DHEA) and its sulfate (DHEAS). Objective: To characterize the clinical and molecular features of this case and to determine whether the tissue biochemically resembles the Zona Reticularis or fetal adrenal. Setting: University clinic, hospital, and laboratories. Design: Static and dynamic blood and urine testing were performed preoperatively. Tissue was studied by light microscopy, immunoblot, RNA microarray, and enzyme assay. Participant: A 29-year-old man with incidentally discovered bilateral adrenal enlargement. Intervention: Bilateral adrenalectomy. Main Outcome Measures: Molecular studies compared with control samples. Results: Hypercortisolism and 21-hydroxylase deficiency were excluded. DHEA, DHEAS, and 17-hydroxypregnenolone were markedly elevated and did not suppress with dexamethasone 2 mg/d for 4 days. Homogenates of the adrenals demonstrated high 17-hydroxylase, good 17,20-lyase, and low or absent 21-hydroxylase and 3β-hydroxysteroid dehydrogenase activities. Immunoblots confirmed robust expression of cytochrome P450c17 and AKR1C3 but not P450c21. Microarray analysis demonstrated high CYP11A1 and CYP17A1 expression but low or absent HSD3B1, HSD3B2, and CYP21A2 expression. Expression of mRNA for cytochrome b5 (CYB5A) and AKR1C3, markers of the Zona Reticularis, were markedly elevated. Conclusion: This is the first case of macronodular hyperplasia of the adrenal Zona Reticularis confirmed with studies of enzyme activity, mRNA expression, and protein identification. We speculate that this condition can be clinically silent in men but might cause severe hyperandrogenemia in women.

  • Clinical, Biochemical, and Molecular Characterization of Macronodular Adrenocortical Hyperplasia of the Zona Reticularis: A New Syndrome
    The Journal of Clinical Endocrinology and Metabolism, 2010
    Co-Authors: Hans K. Ghayee, Juilee Rege, William E. Rainey, Lori M Watumull, Fiemu E. Nwariaku, Kelley S. Carrick, Walter L. Miller, Richard J. Auchus
    Abstract:

    The clinical, biochemical, and molecular features of macronodular adrenocortical hyperplasia of the Zona Reticularis in a man are described and characterized.

  • Clinical, biochemical, and molecular characterization of macronodular adrenocortical hyperplasia of the Zona Reticularis: a new syndrome.
    The Journal of clinical endocrinology and metabolism, 2010
    Co-Authors: Hans K. Ghayee, Juilee Rege, William E. Rainey, Lori M Watumull, Fiemu E. Nwariaku, Kelley S. Carrick, Walter L. Miller, Richard J. Auchus
    Abstract:

    Macronodular adrenocortical hyperplasia classically presents with progressive hypercortisolemia and Cushing syndrome. We describe a 29-yr-old man with massive macronodular adrenocortical hyperplasia without hypercortisolemia but rather markedly elevated and nonsuppressible production of dehydroepiandrosterone (DHEA) and its sulfate (DHEAS). To characterize the clinical and molecular features of this case and to determine whether the tissue biochemically resembles the Zona Reticularis or fetal adrenal. University clinic, hospital, and laboratories. Static and dynamic blood and urine testing were performed preoperatively. Tissue was studied by light microscopy, immunoblot, RNA microarray, and enzyme assay. A 29-yr-old man with incidentally discovered bilateral adrenal enlargement. Bilateral adrenalectomy. Molecular studies compared with control samples. Hypercortisolism and 21-hydroxylase deficiency were excluded. DHEA, DHEAS, and 17-hydroxypregnenolone were markedly elevated and did not suppress with dexamethasone 2 mg/d for 4 d. Homogenates of the adrenals demonstrated high 17-hydroxylase, good 17,20-lyase, and low or absent 21-hydroxylase and 3β-hydroxysteroid dehydrogenase activities. Immunoblots confirmed robust expression of cytochrome P450c17 and AKR1C3 but not P450c21. Microarray analysis demonstrated high CYP11A1 and CYP17A1 expression but low or absent HSD3B1, HSD3B2, and CYP21A2 expression. Expression of mRNA for cytochrome b(5) (CYB5A) and AKR1C3, markers of the Zona Reticularis, were markedly elevated. This is the first case of macronodular hyperplasia of the adrenal Zona Reticularis confirmed with studies of enzyme activity, mRNA expression, and protein identification. We speculate that this condition can be clinically silent in men but might cause severe hyperandrogenemia in women.

Peter J. Hornsby - One of the best experts on this subject based on the ideXlab platform.

  • identification of α enolase as a nuclear dna binding protein in the Zona fasciculata but not the Zona Reticularis of the human adrenal cortex
    Journal of Endocrinology, 2005
    Co-Authors: Weiye Wang, Akira Endoh, L Wang, Geoffrey Hummelke, Christina L Hawks, Peter J. Hornsby
    Abstract:

    In order to establish whether there are differences in DNA-binding proteins between Zona fasciculata (ZF) and Zona Reticularis (ZR) cells of the human adrenal cortex, we prepared nuclear extracts from separated ZF and ZR cells. The formation of DNA–protein complexes was studied using an element in the first intron of the type I and type II 3-hydroxysteroid dehydrogenase genes (HSD3B1 and HSD3B2). Using the element in the HSD3B2 gene as a probe, a complex (C1) was formed with extracts from ZF cells but was formed only at a low level with ZR cell extracts. Another pair of complexes (C2/C3) was formed with both ZF and ZR cell extracts. The ZF-specific protein forming C1 was enriched by column chromatography on DEAE-Sepharose and carboxymethylSepharose. Oligonucleotide competition analysis on the enriched fraction gave results consistent with those obtained on the unfractionated material. A further enrichment was brought about by passing the protein over an oligonucleotide affinity column based on the HSD3B2 element. The protein bound to the column was identified as -enolase by mass spectrometry. Although -enolase is a glycolytic enzyme, it binds to specific DNA sequences and has been found to be present in nuclei of various cell types. We performed immunohistochemistry on sections of adult human adrenal cortex and found -enolase to be located in nuclei of ZF cells but to be predominantly cytoplasmic in ZR cells. Transfection of an -enolase expression vector into NCI-H295R human adrenocortical cells increased HSD3B2 promoter activity, suggesting a possible functional role for this protein in regulation of HSD3B2 expression.

  • Aging of the Human Adrenal Cortex
    Science of aging knowledge environment : SAGE KE, 2004
    Co-Authors: Peter J. Hornsby
    Abstract:

    Page 1 The most striking age-related change in the human adrenal cortex is the decline in secretion of dehydroepiandrosterone and its sulfate, steroids synthesized by the inner zone of the cortex, the Zona Reticularis. Because these steroids are of essentially unknown function, the importance of this age-related change is the subject of considerable debate. It is likely that the age-related change in these steroids results from loss of Zona Reticularis cells or impairment of their function. During aging, cumulative damage to the Zona Reticularis could occur through ischemia-related infarcts and other causes of cell death. Cellular senescence could contribute to a loss of the ability of the tissue to replace lost cells. In contrast, feedback mechanisms that regulate adrenocortical growth cause compensatory local tissue hyperplasias called nodules. The effect of imperfect repair of damage combined with compensatory overgrowth in the form of nodules leads to an increasingly abnormal tissue architecture.

  • Differentially expressed genes in Zona Reticularis cells of the human adrenal cortex.
    Molecular and Cellular Endocrinology, 2001
    Co-Authors: Weiye Wang, Peter R. Casson, Lianqing Yang, Tetsuya Suwa, Peter J. Hornsby
    Abstract:

    The Zona Reticularis (ZR) cell in the human adrenal cortex is responsible for the secretion of dehydroepiandrosterone, but its biology, origin, and putative decrease in number during aging are poorly understood. In the present experiments, we investigated to what extent ZR and Zona fasciculata (ZF) cells differ in patterns of gene expression. Both cell types were purified by microdissection from adult adrenal cortex specimens. After a brief period in culture, RNA was harvested from the cells and used to prepare radioactively labeled probes following amplification by PCR. Probes were used in hybridizations of arrays of cDNAs on nylon membranes (PCR products or plasmids obtained from an adrenal cDNA library). Analysis of hybridization intensities showed that 17 of the 750 genes studied differed in expression by more than 2-fold. Several genes expressed at higher levels in ZR cells encode components of the major histocompatibility complex or enzymes involved in peroxide metabolism. Members of the tubulin gene family were expressed at higher levels in ZF cells. Differential expression of four of the genes was confirmed by Northern blotting. These differences show that although ZR and ZF cells are similar in gene expression, ZR cells have a gene expression pattern related to the unique biology of this cell type.

  • Human Adrenal Androgens: Regulation of Biosynthesis and Role in Estrogen-Responsive Breast Cancer in a Mouse Model.
    1999
    Co-Authors: Peter J. Hornsby
    Abstract:

    Abstract : These experiments investigate a mouse model for the biosynthesis of the human adrenal androgens (dehydroepiandrosterone, DHEA, and its sulfate, DHEAS) and the role of these steroids in human breast cancer growth. An androgen-dependent human breast cancer model was established in immunodeficient (scid) mice. Zona Reticularis cells in the human adrenal cortex are responsible for adrenal androgen biosynthesis because of the suppressed expression of 3 beta-hydroxysteroid dehydrogenase (3beta-HSD) in these cells. A protein present in the non-DHEA-secreting zones of the cortex and absent from the Zona Reticularis which binds to a regulatory region of the type II 3 beta-HSD gene was partially purified. Human adrenocortical cells were transplanted into scid mice and were shown to replace the animals own adrenal function. Although Zona Reticularis cells were transplanted, DHEAS was not detected in mouse plasma. As an alternative to the use of human Zona Reticularis cells, clonal bovine adrenocortical cells were shown to be capable of forming tissue in scid mice that replaces the animals adrenal glands. This was shown both with normal clonal cells and with cells genetically modified by the insertion of marker genes. The ability to genetically modify the cells provides a means to test whether suppression of 3 beta-HSD by an antisense strategy can create a tissue with a very high rate of DHEA biosynthesis in the mouse transplant model.

  • The Zona Reticularis is the site of biosynthesis of dehydroepiandrosterone and dehydroepiandrosterone sulfate in the adult human adrenal cortex resulting from its low expression of 3 beta-hydroxysteroid dehydrogenase.
    The Journal of clinical endocrinology and metabolism, 1996
    Co-Authors: Akira Endoh, Sonja B. Kristiansen, Peter R. Casson, John E. Buster, Peter J. Hornsby
    Abstract:

    Based on indirect evidence, it has often been assumed that the Zona Reticularis of the adult human adrenal cortex is the source of the adrenal androgens, dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS), but direct tests of this concept have been few. Using the techniques of cell culture, Northern blotting, and RIA, we compared the properties of separated adult Zonal cells to those of fetal zone cells, a cell type well known to secrete large amounts of DHEA(S) due to its low expression of 3 beta-hydroxysteroid dehydrogenase (3 beta HSD). In nine glands from donors of a wide age range, the Zona fasciculata and Zona Reticularis were separated and dissociated, and the cells were placed in culture. After 5 days, serum was removed by a 24-h period in serum-free defined medium followed by a 24-h exposure to cAMP analogs, with the optional addition of insulin, also in serum-free medium. The separated fasciculata and Reticularis cells showed large differences in the DHEA(S)/cortisol (F) production ratios fr...

Ann D. Nguyen - One of the best experts on this subject based on the ideXlab platform.

  • 1 Morphological Adrenarche in Rhesus Macaques: Development of the Zona Reticularis is Concurrent with Fetal Zone Regression in the Early Neonatal Period
    2016
    Co-Authors: Ann D. Nguyen, Samantha Mapes, Jo C Corbin, Alan J Conley
    Abstract:

    Human adrenarche is associated with the establishment of a functional Zona Reticularis (ZR) and increasing secretion of dehydroepiandrosterone (DHEA) in sulphated form (DS). Like most non-human primates, rhesus macaques are not believed to undergo adrenarche, though they clearly establish a functional ZR after birth. However, the origins of the rhesus ZR are not well defined. Therefore, we investigated the Zonal development, steroidogenic enzyme expression and morphology of rhesus adrenals from 20 1 day to 14 months of age. Immuno-histochemistry was conducted to determine expression profiles of the steroidogenic enzymes 17α-hydroxylase/17,20-lyase cytochrome P450 (P450c17), 21-hydroxylase cytochrome P450 (P450c21), 3β-hydroxysteroid dehydrogenase/∆5-4 isomerase (3β-HSD), the redox partner NADPH-cytochrome P450 oxidoreductase (CPR), as well as the accessory protein cytochrome b5 (b5), a marker of the primate ZR. The rhesus ZR is mature by 3 months of age based on differentiation of the innermost zone which lacks 3β-HSD, but exhibits increased b5 expression during this period. Further, the ZR develops in neonates from a previously described dense band of cells which we show expresses b5, P450c17, CPR, and P450c21 throughout maturation. The fetal zone (FZ) is distinguished from the ZR by its lack of 30 P450c21, and ZR development proceeded as the FZ regressed with two important implications: neither FZ regression nor ZR maturation can be monitored independently by circulating adrenal androgens, and these events must be induced by different factors in rhesus, and likely humans. Collectively, these data demonstrate that ZR development begins before birth in the rhesus, proceeding concomitant with FZ regression post

  • Morphological adrenarche in rhesus macaques: development of the Zona Reticularis is concurrent with fetal zone regression in the early neonatal period
    Journal of Endocrinology, 2008
    Co-Authors: Ann D. Nguyen, Samantha Mapes, C. Jo Corbin, Alan J Conley
    Abstract:

    Human adrenarche is associated with the establishment of a functional Zona Reticularis (ZR) and increasing secretion of dehydroepiandrosterone (DHEA) in sulfated form (DS). Like most non-human primates, rhesus macaques are not believed to undergo adrenarche, though they clearly establish a functional ZR after birth. However, the origins of the rhesus ZR are not well defined. Therefore, we investigated the Zonal development, steroidogenic enzyme expression and morphology of rhesus adrenals from 1 day to 14 months of age. Immunohistochemistry was conducted to determine expression profiles of the steroidogenic enzymes 17alpha-hydroxylase/17,20-lyase cytochrome P450, family 17, subfamily A, polypeptide 1 (CYP17A1), cytochrome P450, family 21, subfamily A, polypeptide 2 (CYP21A2), hydroxy-Delta-5-steroid dehydrogenase, 3beta- and steroid Delta-isomerase 2 (HSD3B2), the redox partner NADPH-cytochrome P450 oxidoreductase (CPR), as well as the accessory protein cytochrome b5 (b5), a marker of the primate ZR. The rhesus ZR is mature by 3 months of age based on differentiation of the innermost zone that lacks HSD3B2, but exhibits increased b5 expression during this period. Further, the ZR develops in neonates from a previously described dense band of cells which we show expresses b5, CYP17A1, CPR, and CYP21A2 throughout maturation. The fetal zone (FZ) is distinguished from the ZR by its lack of CYP21A2, and ZR development proceeded as the FZ regressed with two important implications: neither FZ regression nor ZR maturation can be monitored independently by circulating adrenal androgens, and these events must be induced by different factors in rhesus, and likely humans. Collectively these data demonstrate that ZR development begins before birth in the rhesus, proceeding concomitantly with FZ regression post-natally, suggesting that rhesus experiences morphological adrenarche during the first three months of life.

  • Male marmoset monkeys express an adrenal fetal zone at birth, but not a Zona Reticularis in adulthood.
    Endocrinology, 2004
    Co-Authors: J. Christina Pattison, Ann D. Nguyen, Alan J Conley, David H. Abbott, Wendy Saltzman, Gary L. Henderson, Hongwu Jing, Christopher R. Pryce, Amy J. Allen, Ian M. Bird
    Abstract:

    Neonatal human males produce high levels of dehydroepiandrosterone (DHEA) and its sulfo-conjugated form (DS) that decline within a few months of birth, due to regression of the adrenal fetal zone (FZ). Adult male humans and rhesus monkeys produce C19 steroids in abundance from the adrenal Zona Reticularis (ZR). Male marmoset monkeys produce DS at birth, but unlike humans and rhesus monkeys, do not produce comparable amounts of DHEA and DS in adulthood. To determine whether male marmosets express a functional ZR in adulthood, we examined adult and neonatal male marmosets for the presence of a ZR and FZ, respectively. Exogenous ACTH failed to stimulate DHEA or DS in adults, and dexamethasone treatment failed to suppress DHEA and DS, although cortisol levels changed as expected. In steroidogenic tissues, the key proteins necessary to synthesize C19 steroids from pregnenolone are P450c17, 3beta-hydroxysteroid dehydrogenase (3beta-HSD), nicotinamide adenine dinucleotide phosphate (reduced) oxido-reductase cytochrome P450 (reductase), and cytochromeb5 (cytb5). Adult adrenal cross sections showed P450c17 and reductase protein expression throughout the cortex but showed no expected decrease in 3beta-HSD and increase in cytb5 in the innermost region. Western analysis confirmed these data, demonstrating comparable P450c17 expression to rhesus monkeys, but not cytb5. HPLC analysis revealed similar 17alpha-hydroxylase action on pregnenolone for adult marmoset and rhesus adrenal microsomes but greatly diminished 17,20-lyase activity in marmosets. Neonatal marmoset adrenals exhibited staining indicative of a putative FZ (with P450c17, reduced 3beta-HSD and increased cytb5). We conclude that neonatal marmosets exhibit a C19 steroid-secreting FZ similar to humans, but adult males fail to acquire a functional ZR.

Ian M. Bird - One of the best experts on this subject based on the ideXlab platform.

  • In the zone: understanding Zona Reticularis function and its transformation by adrenarche.
    The Journal of endocrinology, 2012
    Co-Authors: Ian M. Bird
    Abstract:

    The human adrenal cortex comprises three distinct zones with unique steroid products, namely the Zona glomerulosa, which secretes the mineralocorticoids, the Zona fasciculate, which secretes the glucocorticoids and the Zona Reticularis (ZR), which at adrenarche, begins to produce the so-called adrenal androgens. Of all the adrenal zones, we still understand control of ZR emergence the least, and yet the consequences of such dysregulation can be devastating. Premature adrenarche is a growing problem and the correspondingly inappropriate emergence of ZR function can negatively influence puberty and lead to adult infertility. Our understanding is limited and more needs to be done. The purpose of these three reviews is to provide a survey of where we are in our current understanding of what adrenarche is, and indeed if it is unique to humans at all. Furthermore, these reviews describe what is also known of how the functional ZR emerges during adrenarche and what steroids of physiologic relevance result beyond the widely known DHEA and DHEAS elevated at this time. Such advances in human, primate and indeed stem-cell biology are clearly laying the foundation for new directions in the hunt for the factors involved in the regulation and functional emergence of a ZR at the appropriate time, as well as insight into how they may fail. Given support for these new directions, considerable progress can clearly be made.

  • Plasticity of the Zona Reticularis in the adult marmoset adrenal cortex: voyages of discovery in the New World.
    The Journal of endocrinology, 2009
    Co-Authors: J. Christina Pattison, Alan J Conley, David H. Abbott, Wendy Saltzman, Ian M. Bird
    Abstract:

    Adrenarche in humans occurs at the age of 5–7 years, yet the process by which dehydroepiandrosterone (DHEA) biosynthesis in the adrenal Zona Reticularis (ZR) increases so dramatically remains as a matter of debate. One suggestion is that increased DHEA production by P450c17 (CYP17A1 as listed in HUGO Database) in the ZR results from a coincident fall in the expression of HSD3B, which would otherwise compete for pregnenolone substrate. Nonetheless, studies of human and rhesus adrenal show that cytochrome b5 (CYTB5) expression increases in the ZR with DHEA biosynthesis, and cloned human and rhesus P450c17 show selective increases in 17,20-lyase activity in the presence of CYTB5. The marmoset, a New World primate, expresses a fetal zone during development which regresses after birth. Adult males, however, do not develop an obvious functional ZR, while females develop a ZR in a manner that depends on their social/gonadal status. In all social and physiologic states, changes in marmoset ZR function relate directly to changes in the expression of CYTB5. Recent cloning and expression of marmoset P450c17 also show that while amino acid sequence homology is in the order ofw85% of that found in human and rhesus sequences, and basal lyase activity is low compared with rhesus, all previously described amino acids critical to human 17,20-lyase activity are completely conserved. Furthermore, the 17,20-lyase activity of the marmoset P450c17 clone is dramatically increased by addition of CYTB5. We propose that these combined data from the marmoset model provide further compelling evidence that the control of ZR CYTB5 expression is a key determinant of ZR function.

  • Male marmoset monkeys express an adrenal fetal zone at birth, but not a Zona Reticularis in adulthood.
    Endocrinology, 2004
    Co-Authors: J. Christina Pattison, Ann D. Nguyen, Alan J Conley, David H. Abbott, Wendy Saltzman, Gary L. Henderson, Hongwu Jing, Christopher R. Pryce, Amy J. Allen, Ian M. Bird
    Abstract:

    Neonatal human males produce high levels of dehydroepiandrosterone (DHEA) and its sulfo-conjugated form (DS) that decline within a few months of birth, due to regression of the adrenal fetal zone (FZ). Adult male humans and rhesus monkeys produce C19 steroids in abundance from the adrenal Zona Reticularis (ZR). Male marmoset monkeys produce DS at birth, but unlike humans and rhesus monkeys, do not produce comparable amounts of DHEA and DS in adulthood. To determine whether male marmosets express a functional ZR in adulthood, we examined adult and neonatal male marmosets for the presence of a ZR and FZ, respectively. Exogenous ACTH failed to stimulate DHEA or DS in adults, and dexamethasone treatment failed to suppress DHEA and DS, although cortisol levels changed as expected. In steroidogenic tissues, the key proteins necessary to synthesize C19 steroids from pregnenolone are P450c17, 3beta-hydroxysteroid dehydrogenase (3beta-HSD), nicotinamide adenine dinucleotide phosphate (reduced) oxido-reductase cytochrome P450 (reductase), and cytochromeb5 (cytb5). Adult adrenal cross sections showed P450c17 and reductase protein expression throughout the cortex but showed no expected decrease in 3beta-HSD and increase in cytb5 in the innermost region. Western analysis confirmed these data, demonstrating comparable P450c17 expression to rhesus monkeys, but not cytb5. HPLC analysis revealed similar 17alpha-hydroxylase action on pregnenolone for adult marmoset and rhesus adrenal microsomes but greatly diminished 17,20-lyase activity in marmosets. Neonatal marmoset adrenals exhibited staining indicative of a putative FZ (with P450c17, reduced 3beta-HSD and increased cytb5). We conclude that neonatal marmosets exhibit a C19 steroid-secreting FZ similar to humans, but adult males fail to acquire a functional ZR.