Central role for corticosteroid-binding globulin in rat HPA axis sexual dimorphism

2019 ◽  
Author(s):  
Julia Toews ◽  
Lesley Hill ◽  
Tristan Philippe ◽  
Juilee Rege ◽  
William Rainey ◽  
...  
Keyword(s):  
Sexual Dimorphism ◽  
Hpa Axis ◽  
Corticosteroid Binding Globulin

scholarly journals Liver at the nexus of rat postnatal HPA axis maturation and sexual dimorphism

2021 ◽  
Vol 248 (1) ◽  
pp. R1-R17
Author(s):  
Julia N C Toews ◽  
Geoffrey L Hammond ◽  
Victor Viau
Keyword(s):  
Sexual Dimorphism ◽  
Hpa Axis ◽  
Mammalian Species ◽  
Normal Function ◽  
Expression Of Genes ◽  
Corticosteroid Binding Globulin ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis ◽  
Context Specific

Normal function of the hypothalamic–pituitary–adrenal (HPA) axis is critical for survival, and its development is choreographed for age-, sex- and context-specific actions. The liver influences HPA ontogeny, integrating diverse endocrine signals that inhibit or activate its development. This review examines how developmental changes in the expression of genes in the liver coordinate postnatal changes in multiple endocrine systems that facilitate the maturation and sexual dimorphism of the rat HPA axis. Specifically, it examines how the ontogeny of testicular androgen production, somatostatin-growth hormone activities, and hypothalamic-pituitary-thyroid axis activity intersect to influence the hepatic gene expression of insulin-like growth factor 1, corticosteroid-binding globulin, thyroxine-binding globulin, 11β-hydroxysteroid dehydrogenase type 1 and 5α-reductase type 1. The timing of such molecular changes vary between mammalian species, but they are evolutionarily conserved and are poised to control homeostasis broadly, especially during adversity. Importantly, with the liver as their nexus, these diverse endocrine systems establish the fundamental organization of the HPA axis throughout postnatal development, and thereby ultimately determine the actions of glucocorticoids during adulthood.

Sexual dimorphism in the hypothalamo-pituitary-adrenal (HPA) axis and TNFα responses to phospholipase A2-related neurotoxin (from crotalus durissus terrificus) challenge

2000 ◽  
Vol 23 (7) ◽  
pp. 440-448 ◽  
Author(s):  
A. N. Chisari ◽  
R. C. Gaillard ◽  
A. Giovambattista ◽  
M.-J. Voirol ◽  
J. Piermaría ◽  
...  
Keyword(s):  
Sexual Dimorphism ◽  
Phospholipase A2 ◽  
Hpa Axis ◽  
Crotalus Durissus Terrificus ◽  
Crotalus Durissus

Behavioral sexual dimorphism in models of anxiety and depression due to changes in HPA axis activity

2012 ◽  
Vol 62 (1) ◽  
pp. 436-445 ◽  
Author(s):  
Nikolaos Kokras ◽  
Christina Dalla ◽  
Antonios C. Sideris ◽  
Artemis Dendi ◽  
Hudu G. Mikail ◽  
...  
Keyword(s):  
Sexual Dimorphism ◽  
Hpa Axis ◽  
Anxiety And Depression ◽  
Hpa Axis Activity

scholarly journals Somatostatin Is Essential for the Sexual Dimorphism of GH Secretion, Corticosteroid-Binding Globulin Production, and Corticosterone Levels in Mice

Endocrinology ◽  
2015 ◽  
Vol 156 (3) ◽  
pp. 1052-1065 ◽  
Author(s):  
Jessica M. Adams ◽  
Veronica Otero-Corchon ◽  
Geoffrey L. Hammond ◽  
Johannes D. Veldhuis ◽  
Nathan Qi ◽  
...  
Keyword(s):  
Sexual Dimorphism ◽  
Peak Plasma ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Plasma Corticosterone ◽  
Automated System ◽  
Sexually Dimorphic ◽  
Mrna Levels ◽  
Gh Secretion ◽  
Corticosteroid Binding Globulin

Abstract Distinct male and female patterns of pituitary GH secretion produce sexually differentiated hepatic gene expression profiles, thereby influencing steroid and xenobiotic metabolism. We used a fully automated system to obtain serial nocturnal blood samples every 15 minutes from cannulated wild-type (WT) and somatostatin knockout (Sst-KO) mice to determine the role of SST, the principal inhibitor of GH release, in the generation of sexually dimorphic GH pulsatility. WT males had lower mean and median GH values, less random GH secretory bursts, and longer trough periods between GH pulses than WT females. Each of these parameters was feminized in male Sst-KO mice, whereas female Sst-KO mice had higher GH levels than all other groups, but GH pulsatility was unaffected. We next performed hepatic mRNA profiling with high-density microarrays. Male Sst-KO mice exhibited a globally feminized pattern of GH-dependent mRNA levels, but female Sst-KO mice were largely unaffected. Among the differentially expressed female-predominant genes was Serpina6, which encodes corticosteroid-binding globulin (CBG). Increased CBG was associated with elevated diurnal peak plasma corticosterone in unstressed WT females and both sexes of Sst-KO mice compared with WT males. Sst-KO mice also had exaggerated ACTH and corticosterone responses to acute restraint stress. However, consistent with their lack of phenotypic signs of excess glucocorticoids, cerebrospinal fluid concentrations of free corticosterone in Sst-KO mice were not elevated. In summary, SST is necessary for the prolonged interpulse troughs that define masculinized pituitary GH secretion. SST also contributes to sexual dimorphism of the hypothalamic-pituitary-adrenal axis via GH-dependent regulation of hepatic CBG production.

scholarly journals Corticosteroid-Binding Globulin is expressed in the adrenal gland and its absence impairs corticosterone synthesis and secretion in a sex-dependent manner

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
José Gulfo ◽  
Ricard Castel ◽  
Angelo Ledda ◽  
María del Mar Romero ◽  
Montserrat Esteve ◽  
...  
Keyword(s):  
Sexual Dimorphism ◽  
Adrenal Gland ◽  
Synthetic Activity ◽  
Dependent Manner ◽  
Adrenal Hormones ◽  
Corticosteroid Binding Globulin ◽  
Relevant Role ◽  
Response To Stress ◽  
Hormone Control

Abstract Corticosteroid-binding globulin (CBG) is synthesized by the liver and secreted into the bloodstream where binds to glucocorticoids. Thus CBG has the role of glucocorticoid transport and free hormone control. In addition, CBG has been detected in some extrahepatic tissues without a known role. CBG-deficient mice show decreased total corticosterone levels with missing of classical sexual dimorphism, increased free corticosterone, higher adrenal gland size and altered HPA axis response to stress. Our aim was to ascertain whether CBG deficiency could affect the endocrine synthetic activity of adrenal gland and if the adrenal gland produces CBG. We determined the expression in adrenal gland of proteins involved in the cholesterol uptake and its transport to mitochondria and the main enzymes involved in the corticosterone, aldosterone and catecholamine synthesis. The results showed that CBG is synthesized in the adrenal gland. CBG-deficiency reduced the expression of ACTH receptor, SRB1 and the main genes involved in the adrenal hormones synthesis, stronger in females resulting in the loss of sexual dimorphism in corticosteroid adrenal synthesis, despite corticosterone content in adrenal glands from CBG-deficient females was similar to wildtype ones. In conclusion, these results point to an unexplored and relevant role of CBG in the adrenal gland functionality related to corticosterone production and release.

scholarly journals SUN-LB082 Sexual Dimorphism of Phosphoethanolamine in HPA-Axis Response to LXR Agonist 25-Hydroxycholesterol: Neuroendocrine Implications for Major Depressive Disorder

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Douglas Osei-Hyiaman ◽  
Aya Hoshi ◽  
Kaori Honda-Hanawa ◽  
Hajime Tomatsu ◽  
Resat Cinar ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Sexual Dimorphism ◽  
Depressive Disorder ◽  
Hpa Axis ◽  
Major Depressive

Stimulatory effect of interleukin-1β on the hypothalamic-pituitary-adrenal axis of the rat: influence of age, gender and circulating sex steroids

1994 ◽  
Vol 140 (3) ◽  
pp. 365-372 ◽  
Author(s):  
C Rivier
Keyword(s):  
Sexual Dimorphism ◽  
Hpa Axis ◽  
Sex Steroids ◽  
Absolute Amount ◽  
Sexually Dimorphic ◽  
Acth Secretion ◽  
Stimulatory Action ◽  
Hypothalamic Pituitary Adrenal ◽  
Adrenal Response ◽  
Old Rats

Abstract The bilateral communication between the immune and neuroendocrine systems plays an essential role in modulating the adequate response of the hypothalamic-pituitary-adrenal (HPA) axis to the stimulatory influence of interleukins (ILs). It is thus reasonable to assume that inappropriate responses of the HPA axis to ILs might play a role in modulating the onset of pathological conditions such as infections. As part of our programme aimed at investigating the ability of ILs to release pro-opiomelanocortin-like peptides and corticosterone in rats exposed to alcohol, we observed that this stimulatory action appeared to be influenced by the gender of the animals. We therefore examined the ability of IL-1β, injected peripherally, to stimulate the HPA axis as a function of stage of sexual maturation and the presence or absence of circulating sex steroids. In immature (21 to 22-day-old) rats, both males and females responded to the i.p. administration of 0·5 or 2·0 μg IL-1β/kg with statistically comparable increases in plasma ACTH levels. In contrast, females released significantly (P<0·01) more corticosterone in response to the lower dose of cytokine. Forty-day-old intact animals showed no sexual dimorphism in ACTH secretion, but the females again secreted significantly (P<0·05–0·01) more corticosterone. Gonadectomy, performed 7–8 days prior to the assay, increased the absolute amount of corticosterone released over a 60-min period. A noticeable dimorphism of the ACTH response to IL-1β became apparent in 70-day-old intact rats, with females secreting more ACTH than males. These females also released significantly more corticosterone than males under both resting and stimulated circumstances. In this age group, gonadectomy abolished the sex difference in terms of ACTH release, but augmented the total amount of corticosteroids secreted by both sexes, as well as increasing the sexual dimorphism. These results suggest the presence of gender differences in the response of the HPA axis to IL-1β. While the sexual dimorphism of ACTH secretion appears to be dependent on circulating sex steroids, the sexually dimorphic adrenal response was retained following gonadectomy. Journal of Endocrinology (1994) 140, 365–372

scholarly journals Strain differences in hypothalamic–pituitary–adrenocortical axis function and adipogenic effects of corticosterone in rats

2007 ◽  
Vol 195 (3) ◽  
pp. 473-484 ◽  
Author(s):  
Nathalie Marissal-Arvy ◽  
Alexandra Gaumont ◽  
Allan Langlois ◽  
Fabrice Dabertrand ◽  
Marion Bouchecareilh ◽  
...  
Keyword(s):  
Body Weight ◽  
Hpa Axis ◽  
Fat Mass ◽  
Healthy Aging ◽  
Body Weight Gain ◽  
Strain Differences ◽  
Fischer 344 ◽  
Diet Induced Obesity ◽  
Corticosteroid Binding Globulin ◽  
Rat Strain

Our aim was to explore the nutritional consequences of functional variations in the hypothalamic–pituitary–adrenocortical (HPA) axis in rats. We first aimed to compare the HPA axis activity and reactivity to stress between Fischer 344 (F344) and LOU/C (LOU) strains that differ in food behavior and metabolism. When compared with F344 rats, LOU rats showed lower corticosterone (Cort) levels across the circadian cycle and after restraint stress. Then, we compared the effects of adrenalectomized (ADX) and Cort substitution after ADX on food intake, body weight gain, body composition, and biochemical parameters related to metabolism and HPA axis function between 1) the F344 rat strain, a model of HPA axis hyperactivity and hyperreactivity to stress, and characterized by a large fat mass; 2) the LOU strain, shown to exhibit hypoactive/hyporeactive HPA axis, reduced fat mass, and resistance to diet-induced obesity; and 3) the Lewis (LEW) strain, a third condition of fat deposition (high) related to HPA axis function (low activity/reactivity). The F344 and LEW strains exhibited classical responses to ADX and Cort. On the contrary, LOU rats showed an apparent insensitivity to ADX. Despite the highest effects of Cort related to glucocorticoid receptor (on thymus weight, corticotropin-releasing factor, or corticosteroid-binding globulin), the LOU strain was insensitive to Cort effects on body weight, liver, and abdominal fat mass. These characteristics could be involved in the leanness, insensitivity to diet-induced obesity, and healthy aging in LOU. Our study shows the relevance of comparing the F344, LOU, and LEW strains to cover the complexity of interactions between metabolism and HPA axis function.

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