Sex dimorphic changes in Trh gene methylation and thyroid-axis response to energy demands in maternally-separated rats

Endocrinology ◽  
2021 ◽  
Author(s):  
Lorraine Jaimes-Hoy ◽  
Adrián Pérez-Maldonado ◽  
Elian Narváez Bahena ◽  
Natalia de la Cruz Guarneros ◽  
Adair Rodríguez-Rodríguez ◽  
...  

Abstract The hypothalamus-pituitary-thyroid (HPT) axis regulates energy balance through the pleiotropic action of thyroid hormones. HPT basal activity and stimulation by cold or voluntary exercise are repressed by previous chronic stress in adults. Maternal separation (MS) modifies HPT basal activity, we thus studied the response of the axis to energy demands and analyzed possible epigenetic changes on Trh promoter. Non-handled (NH) or MS male Wistar rats were cold exposed 1h at adulthood, only in NH rats Trh expression in the hypothalamic paraventricular nucleus (PVN) and serum TSH concentration were increased. Two weeks of voluntary exercise decreased fat mass, increased Trh expression, and thyroid hormones concentration changed proportionally to running distance in NH male rats and MS male rats. Although NH-females ran more than MS and much more than males, exercise decreased body weight and fat mass only in NH-rats with no change on any parameter of HPT axis, but increased Pomc expression in arcuate-nucleus of NH- whereas Npy in MS-females. Overall methylation pattern of PVN Trh gene promoter was similar in NH-males or -females; MS modified methylation of specific CpG sites, a thyroid-hormone receptor (THR) binding site present after the initiation site was hypomethylated in MS-males; in MS-females, the THR binding-site of the proximal promoter (site 4) and two sites in the first intron were hypermethylated. Our studies showed that, in a sex dimorphic manner, MS blunted the responses of HPT axis to energy demands in adult animals and caused methylation changes on Trh promoter that could alter T3 feedback.

Endocrinology ◽  
2014 ◽  
Vol 155 (5) ◽  
pp. 2020-2030 ◽  
Author(s):  
Rosa María Uribe ◽  
Lorraine Jaimes-Hoy ◽  
Candy Ramírez-Martínez ◽  
Arlene García-Vázquez ◽  
Fidelia Romero ◽  
...  

The hypothalamic-pituitary thyroid (HPT) axis modulates energy homeostasis. Its activity decreases in conditions of negative energy balance but the effects of chronic exercise on the axis are controversial and unknown at hypothalamic level. Wistar male rats were exposed for up to 14 days to voluntary wheel running (WR), or pair-feeding (PF; 18% food restriction), or to repeated restraint (RR), a mild stressor. WR and RR diminished food intake; body weight gain decreased in the 3 experimental groups, but WAT mass and serum leptin more intensely in the WR group. WR, but not RR, produced a delayed inhibition of central markers of HPT axis activity. At day 14, in WR rats paraventricular nucleus-pro-TRH mRNA and serum TSH levels decreased, anterior pituitary TRH-receptor 1 mRNA levels increased, but serum thyroid hormone levels were unaltered, which is consistent with decreased secretion of TRH and clearance of thyroid hormones. A similar pattern was observed if WR animals were euthanized during their activity phase. In contrast, in PF animals the profound drop of HPT axis activity included decreased serum T3 levels and hepatic deiodinase 1 activity; these changes were correlated with an intense increase in serum corticosterone levels. WR effects on HPT axis were not associated with changes in the activity of the hypothalamic-pituitary adrenal axis, but correlated positively with serum leptin levels. These data demonstrate that voluntary WR adapts the status of the HPT axis, through pathways that are distinct from those observed during food restriction or repeated stress.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Marco Antonio Parra-Montes de Oca ◽  
Angélica Gutiérrez-Mata ◽  
Jean-Louis Charli ◽  
Patricia Joseph-Bravo

Abstract Exposure to chronic stress during adolescence causes long-term effects on the response of Hypothalamus-Pituitary-Adrenal (HPA) axis, affecting behavior and energy homeostasis. Voluntary exercise activates the HP-Thyroid (HPT) axis allowing efficient fluxes of substrates to active target organs. Chronic stress in adult rats blunts HPT axis response to voluntary exercise in a sex-dependent manner (Front Endocrinol 10(418):1-13, 2019). As adolescents show sex-dependent responses to stress, we sought to evaluate the effect of chronic stress at this period in the response of HPT axis to voluntary exercise in adulthood. Wistar male and female rats were divided in an undisturbed group (Control, C) and one group exposed to chronic variable stress (CVS) where the rats were daily subjected to different stressors during postnatal day (PND) 30 to 60 for females and PND 30 to 70 for males. At adulthood (PND 74 for females and PND 84 for males) rats were exposed to running wheel following published protocol (Endocrinology 155:2020-2030, 2014). As females are more susceptible to stress during adolescence than males, additional independent experiments were performed with female rats kept in group or individual housing, since PND 30 (2 per cage or isolated (Iso)). At PND 64, Iso rats were housed in pairs and exposed to CVS every 3 days until PND 80; later, rats were exercised 26 days. Hormones were quantified by ELISA or RIA; mRNA expression was determined by RT-PCR. Voluntary exercise reduced fat mass in C groups, dependent on the amount of exercise performed; stressed rats exercised did not lose fat, indicating that adolescent stress avoids an appropriate energy distribution during exercise. The expression of Crh and Avp in hypothalamic paraventricular nucleus (PVN) decreased in stressed groups mainly in females, as reported. Exercise decreased corticosterone levels only in C rats, suggesting that CVS during adolescence modifies the HPA axis response to exercise. CVS inhibited Pomc expression induced by exercise and increased Npy expression in arcuate nucleus, decreased Trh expression in PVN for both sexes and in dorsomedial hypothalamus in males. Thyroid hormones were not altered in CVS males and Iso females; however, T3 and T4 levels were high in CVS females, so different stress exposures may modify the HPT axis state in females. The response to exercise of the target organs of thyroid hormones reveals with more accuracy the activity of HPT axis, exercise stimulated the expression of Adrb3 and Dio2 in brown adipose tissue of C females, and the expression of Dio2 and Pgc1a in skeletal muscle (gastrocnemius) of both sexes, changes attenuated by CVS. These results indicate that chronic stress during adolescence blunts the response of HPT axis to voluntary exercise, strongly in females than males.


Endocrinology ◽  
2016 ◽  
Vol 157 (8) ◽  
pp. 3253-3265 ◽  
Author(s):  
Lorraine Jaimes-Hoy ◽  
Mariana Gutiérrez-Mariscal ◽  
Yamili Vargas ◽  
Adrián Pérez-Maldonado ◽  
Fidelia Romero ◽  
...  

Hypothalamic-pituitary-thyroid (HPT) axis activity is important for energy homeostasis, and is modified by stress. Maternal separation (MS) alters the stress response and predisposes to metabolic disturbances in the adult. We therefore studied the effect of MS on adult HPT axis activity. Wistar male and female pups were separated from their mothers 3 h/d during postnatal day (PND)2–PND21 (MS), or left nonhandled (NH). Open field and elevated plus maze tests revealed increased locomotion in MS males and anxiety-like behavior in MS females. At PND90, MS females had increased body weight gain, Trh expression in the hypothalamic paraventricular nucleus, and white adipose tissue mass. MS males had increased expression of TRH-degrading enzyme in tanycytes, reduced TSH and T3, and enhanced corticosterone serum concentrations. MS stimulated brown adipose tissue deiodinase 2 activity in either sex. Forty-eight hours of fasting (PND60) augmented serum corticosterone levels similarly in MS or NH females but more in MS than in NH male rats. MS reduced the fasting-induced drop in hypothalamic paraventricular nucleus-Trh expression of males but not of females and abolished the fasting-induced increase in Trh expression in both sexes. Fasting reduced serum concentrations of TSH, T4, and T3, less in MS than in NH males, whereas in females, TSH decreased in MS but not in NH rats, but T4 and T3 decreased similarly in NH and MS rats. In conclusion, MS produced long-term changes in the activity of the HPT axis that were sex specific; response to fasting was partially blunted in males, which could affect their adaptive response to negative energy balance.


2013 ◽  
Vol 10 (4) ◽  
pp. 420-432 ◽  
Author(s):  
Eva Martisova ◽  
Barbara Aisa ◽  
Gorka Guerenu ◽  
Maria Javier Ramirez

2013 ◽  
Vol 56 (5) ◽  
pp. 1102-1109 ◽  
Author(s):  
Xiujing Cao ◽  
Shenghai Huang ◽  
Jiejie Cao ◽  
Tingting Chen ◽  
Ping Zhu ◽  
...  

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
D. M. Sontam ◽  
M. H. Vickers ◽  
J. M. O’Sullivan ◽  
M. Watson ◽  
E. C. Firth

Physical activity has a vital role in regulating and improving bone strength. Responsiveness of bone mass to exercise is age dependent with the prepubertal period suggested to be the most effective stage for interventions. There is a paucity of data on the effects of exercise on bone architecture and body composition when studied within the prepubertal period. We examined the effect of two forms of low-impact exercise on prepubertal changes in body composition and bone architecture. Weanling male rats were assigned to control (CON), bipedal stance (BPS), or wheel exercise (WEX) groups for 15 days until the onset of puberty. Distance travelled via WEX was recorded, food intake measured, and body composition quantified. Trabecular and cortical microarchitecture of the femur were determined by microcomputed tomography. WEX led to a higher lean mass and reduced fat mass compared to CON. WEX animals had greater femoral cortical cross-sectional thickness and closed porosity compared to CON. The different exercise modalities had no effect on body weight or food intake, but WEX significantly altered body composition and femoral microarchitecture. These data suggest that short-term mild voluntary exercise in normal prepubertal rats can alter body composition dependent upon the exercise modality.


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