Endocrine Abstracts

In the healthy liver, GH signals through multiple pathways to modulate hepatic function, with JAK2/STAT5b required to maintain circulating IGF1 levels. It has been previously reported that mice with developmental knockout of hepatocyte GHR, JAK2 or STAT5 develop steatosis associated with glucose intolerance, systemic insulin resistance and white adipose tissue (WAT) lipolysis. These changes are thought to be secondary to increased circulating GH, due to loss of IGF1 negative f...

GH levels decline with age and weight gain and are enhanced in response to nutrient deprivation. Under these circumstances, GH levels are negatively correlated with IGF1 and insulin levels. Since IGF1 and insulin can directly inhibit GH synthesis and release from primary pituitary cells of different species, it is commonly accepted that changes in circulating IGF1 and insulin serve to directly regulate somatotrope function in response to metabolic extremes. However, teasing ap...

Secretion of GH by pituitary somatotropes is primarily stimulated by GHRH and ghrelin and inhibited by SST through the activation of specific receptors (GHRH-R, GHS-R and Sstr1-5, respectively). However, we have previously shown that SST, at low doses, can also stimulate GH release, directly and specifically, in primary pituitary cell cultures from baboons (Papio anubis) and pigs. To determine whether these primary regulators of GH release can also regulate directly the...

Fatty liver (steatosis) can progress to non-alcoholic fatty liver disease, increasing the risk of diabetes and cardiovascular disease. Growth hormone (GH) deficiency is associated with steatosis, while raising GH reduces steatosis. To date it remains to be determined how GH mediates this hepato-protective effect. To investigate the hepatocyte-specific actions of GH, a mouse model of adult-onset hepatocyte-specific GH receptor knockdown (aHepGHRkd) was generated by treating adu...

Liver autophagy, as assessed by accumulation of LC3-II and p62 proteins, is positively correlated with the severity of nonalcoholic steatohepatitis (NASH) in humans. Since growth hormone (GH) is negatively associated with liver steatosis and NASH development, and our laboratory has reported that steatosis and NASH develops in a mouse model of adult-onset, hepatocyte-specific GH-Receptor knockdown (aHepGHRkd), we sought to determine if GH directly regulates the hepatocyte autop...

Kisspeptins (Kp), a peptide family encoded by Kiss1 gene, and their receptor Kiss1r were first identified by their anti-metastatic actions but have emerged as key regulators of the reproductive axis, where they integrate sexual, metabolic and seasonal cues to control hypothalamic GnRH release. Recent data indicates that some actions of Kps may be effected directly at the pituitary (PIT), since Kissr1 is expressed in the PIT and Kp stimulate luteinizing hormone (LH) secretion d...

ESE Young Investigator AwardIntroduction: GH and IGF1 are thought to promote breast carcinogenesis as circulating levels of GH/IGF1 are positively correlated with breast cancer risk in epidemiologic studies, and mouse models with developmental GH/IGF1 deficiency or resistance are less susceptible to breast cancer development. However, no studies have shown that high levels of circulating GH/IGF1 can promote mammary tumorigenesis. In this...

Ghrelin has been classically known as a GH- and metabolism-regulating hormone, mainly produced by stomach. However, it also acts as a paracrine or autocrine factor in several tissues, where it can regulate tissue growth and neoplastic cell proliferation. Of note, ghrelin needs to be acylated at Ser3 by the ghrelin-O-acyltransferase (GOAT) enzyme to bind to its receptor GHS-R1a. Interestingly, the ghrelin gene can give rise to distinct additional peptides, generated by alternat...

The neuropeptide somatostatin (SRIF) exerts a wide variety of actions through five SRIF receptors (sst1-5). However, not all SRIF actions can be explained by activation of the known sst. In this context, our research group has identified two novel isoforms of sst subtype 5 (sst5A) named sst5B and sst5C expressed in human and pig. These isoforms are generated by splicing of cryptic introns within the coding sequence, which alters the open reading frame, and results in new, trun...

Antidiabetic biguanides, such as metformin (the most commonly prescribed drug to treat type 2 diabetes) and phenformin, are synthetic insulin-sensitizing agents. In addition to their well-known anti-hyperglycemic actions, biguanides are being also studied in other medical disorders due to the beneficial effects that they exert in important pathologies, including cardiovascular disease or different types of cancer. Although some scattered studies have suggested that metformin c...