Does the pituitary somatotrope play a primary role in regulating GH output in metabolic extremes?

Luque, Raúl M.; Gahete, Manuel D.; Córdoba-Chacón, José; Childs, Gwen V.; Kineman, Rhonda D.

doi:10.1111/j.1749-6632.2010.05913.x

Cited by 22 publications

(26 citation statements)

References 111 publications

(219 reference statements)

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“…Of note, these changes seemed to be more pronounced under LF conditions, wherein SST-KO and CORT-KO mice exhibited obvious elevated GH levels compared to controls. The fact that these changes were less evident under HF-feeding could be associated to the fact that obesity represents an extreme metabolic status that courses with clear impairments in GH pulses3637, which could be masking the loss of SST/CORT inhibitory effect. Remarkably, these changes in plasma GH levels were not accompanied by parallel alterations in the expression of pituitary GH mRNA, which is consistent with previous reports2527293839 and reinforces the idea that SST and CORT could be exerting regulatory roles at different levels of the regulatory axis of the GH secretion, including the hypothalamic level, the control of secretory pulses or the regulation of other hormonal systems (ghrelin, glucocorticoids, etc.)…”

Section: Discussionmentioning

confidence: 99%

Obesity- and gender-dependent role of endogenous somatostatin and cortistatin in the regulation of endocrine and metabolic homeostasis in mice

Luque

Córdoba-Chacón

Pozo-Salas

et al. 2016

Sci Rep

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Somatostatin (SST) and cortistatin (CORT) regulate numerous endocrine secretions and their absence [knockout (KO)-models] causes important endocrine-metabolic alterations, including pituitary dysregulations. We have demonstrated that the metabolic phenotype of single or combined SST/CORT KO-models is not drastically altered under normal conditions. However, the biological actions of SST/CORT are conditioned by the metabolic-status (e.g. obesity). Therefore, we used male/female SST- and CORT-KO mice fed low-fat (LF) or high-fat (HF) diet to explore the interplay between SST/CORT and obesity in the control of relevant pituitary-axes and whole-body metabolism. Our results showed that the SST/CORT role in the control of GH/prolactin secretions is maintained under LF- and HF-diet conditions as SST-KOs presented higher GH/prolactin-levels, while CORT-KOs displayed higher GH- and lower prolactin-levels than controls under both diets. Moreover, the impact of lack of SST/CORT on the metabolic-function was gender- and diet-dependent. Particularly, SST-KOs were more sensitive to HF-diet, exhibiting altered growth and body-composition (fat/lean percentage) and impaired glucose/insulin-metabolism, especially in males. Conversely, only males CORT-KO under LF-diet conditions exhibited significant alterations, displaying higher glucose-levels and insulin-resistance. Altogether, these data demonstrate a tight interplay between SST/CORT-axis and the metabolic status in the control of endocrine/metabolic functions and unveil a clear dissociation of SST/CORT roles.

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Section: Discussionmentioning

confidence: 99%

Obesity- and gender-dependent role of endogenous somatostatin and cortistatin in the regulation of endocrine and metabolic homeostasis in mice

Luque

Córdoba-Chacón

Pozo-Salas

et al. 2016

Sci Rep

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“…Given insulin can also act directly at the pituitary level to inhibit GH synthesis and release and is thought to contribute to suppressed GH levels observed in obesity (29), studies were conducted to inactivate both the IgfIr and insulin receptor (Insr) genes in pituitary somatotropes. In contrast to somatotropespecific inactivation of IgfIr alone, inactivation of both IgfIr and Insr elevated endogenous GH (2-to 3-fold) and IGF-I (1.2-to 1.4-fold), sufficient to modestly increase linear growth (29). These initial observations confirm that both insulin and IGF-I are important in directly inhibiting GH output from pituitary somatotropes.…”

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confidence: 99%

Elevated GH/IGF-I, Due to Somatotrope-Specific Loss of Both IGF-I and Insulin Receptors, Alters Glucose Homeostasis and Insulin Sensitivity in a Diet-Dependent Manner

et al. 2011

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A unique mouse model was developed with elevated endogenous GH (2- to 3-fold) and IGF-I (1.2- to 1.4-fold), due to somatotrope-specific Cre-mediated inactivation of IGF-I receptor (IgfIr) and insulin receptor (Insr) genes (IgfIr,Insr(rGHpCre), referred to as HiGH mice). We demonstrate that the metabolic phenotype of HiGH mice is diet dependent and differs from that observed in other mouse models of GH excess due to ectopic heterologous transgene expression or pituitary tumor formation. Elevated endogenous GH promotes lean mass and whole-body lipid oxidation but has minimal effects on adiposity, even in response to diet-induced obesity. When caloric intake is moderated, elevated GH improves glucose clearance, despite low/normal insulin sensitivity, which may be explained in part by enhanced IGF-I and insulin output. However, when caloric intake is in excess, elevated GH promotes hepatic lipid accumulation, insulin resistance, hyperglycemia, and ketosis. The HiGH mouse model represents a useful tool to study the role endogenous circulating GH levels play in regulating health and disease.

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“…GH secretion is under complex regulation and modulation by hypothalamic, peripheral and intrapituitary hormones . It will be of interest to determine whether some of these hormones exert their regulatory (or modulatory) action via selective activation (or inhibition) of specific Ca 2+ channel types.…”

Section: Discussionmentioning

confidence: 99%

MultipleCa²⁺Channel‐Dependent Components in Growth Hormone Secretion from Rat Anterior Pituitary Somatotrophs

Sosial

Nussinovitch

2015

J Neuroendocrinology

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The involvement of L-type Ca(2+) channels in both 'basal' and 'stimulated' growth hormone (GH) secretion is well established; however, knowledge regarding the involvement of non-L-type Ca(2+) channels is lacking. We investigated whether non-L-type Ca(2+) channels regulate GH secretion from anterior pituitary (AP) cells. To this end, GH secretion was monitored from dissociated AP cells, which were incubated for 15 min with 2 mm K(+) ('basal' secretion) or 60 mm K(+) ('stimulated' secretion). The role of non-L-type Ca(2+) influx was investigated using specific channel blockers, including ω-agatoxin-IVA, ω-conotoxin GVIA or SNX-482, to block P/Q-, N- or R-type Ca(2+) channels, respectively. Our results demonstrate that P/Q-, N- and R-type Ca(2+) channels contributed 21.2 ± 1.9%, 20.2 ± 7.6% and 11.4 ± 1.8%, respectively, to 'basal' GH secretion and 18.3 ± 1.0%, 24.4 ± 5.4% and 14.2 ± 4.8%, respectively, to 'stimulated' GH secretion. After treatment with a 'cocktail' that comprised the previously described non-L-type blockers, non-L-type Ca(2+) channels contributed 50.9 ± 0.4% and 45.5 ± 2.0% to 'basal' and 'stimulated' GH secretion, respectively. Similarly, based on the effects of nifedipine (10 μM), L-type Ca(2+) channels contributed 34.2 ± 3.7% and 54.7 ± 4.1% to 'basal' and 'stimulated' GH secretion, respectively. Interestingly, the relative contributions of L-type/non-L-type Ca(2+) channels to 'stimulated' GH secretion were well correlated with the relative contributions of L-type/non-L-type Ca(2+) channels to voltage-gated Ca(2+) influx in AP cells. Finally, we demonstrated that compartmentalisation of Ca(2+) channels is important for GH secretion. Lipid raft disruption (methyl-β-cyclodextrin, 10 mm) abrogated the compartmentalisation of Ca(2+) channels and substantially reduced 'basal' and 'stimulated' GH secretion by 43.2 ± 3.4% and 58.4 ± 4.0%, respectively. In summary, we have demonstrated that multiple Ca(2+) channel-dependent pathways regulate GH secretion. The proper function of these pathways depends on their compartmentalisation within AP cell membranes.

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Does the pituitary somatotrope play a primary role in regulating GH output in metabolic extremes?

Cited by 22 publications

References 111 publications

Obesity- and gender-dependent role of endogenous somatostatin and cortistatin in the regulation of endocrine and metabolic homeostasis in mice

Obesity- and gender-dependent role of endogenous somatostatin and cortistatin in the regulation of endocrine and metabolic homeostasis in mice

Elevated GH/IGF-I, Due to Somatotrope-Specific Loss of Both IGF-I and Insulin Receptors, Alters Glucose Homeostasis and Insulin Sensitivity in a Diet-Dependent Manner

MultipleCa²⁺Channel‐Dependent Components in Growth Hormone Secretion from Rat Anterior Pituitary Somatotrophs

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Does the pituitary somatotrope play a primary role in regulating GH output in metabolic extremes?

Cited by 22 publications

References 111 publications

Obesity- and gender-dependent role of endogenous somatostatin and cortistatin in the regulation of endocrine and metabolic homeostasis in mice

Obesity- and gender-dependent role of endogenous somatostatin and cortistatin in the regulation of endocrine and metabolic homeostasis in mice

Elevated GH/IGF-I, Due to Somatotrope-Specific Loss of Both IGF-I and Insulin Receptors, Alters Glucose Homeostasis and Insulin Sensitivity in a Diet-Dependent Manner

MultipleCa2+Channel‐Dependent Components in Growth Hormone Secretion from Rat Anterior Pituitary Somatotrophs

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MultipleCa²⁺Channel‐Dependent Components in Growth Hormone Secretion from Rat Anterior Pituitary Somatotrophs