Download the Free Unbound MEDLINE PubMed App to your smartphone or tablet.
Available for iPhone, iPad, iPod touch, and Android.
- Table of contents. [Journal Article]
- Endocrinology 2014 Nov; 155(11):4A-8A.
- Editorial board. [Journal Article]
- Endocrinology 2014 Nov; 155(11):3A.
- Cover and front matter. [Journal Article]
- Endocrinology 2014 Nov; 155(11):1A-2A.
- Unzipping Androgen Action Through ZIP9: A Novel Membrane Androgen Receptor. [Journal Article]
- Endocrinology 2014 Nov; 155(11):4120-3.
- Duelling receptors: estrogen receptor versus mineralocorticoid receptor in the cardiovascular system. [Journal Article]
- Endocrinology 2014 Nov; 155(11):4117-9.
- Broadening the role of osteocalcin in leydig cells. [Journal Article]
- Endocrinology 2014 Nov; 155(11):4115-6.
- 3,5-Diiodo-L-thyronine (3,5-T2) exerts thyromimetic effects on hypothalamus-pituitary-thyroid axis, body composition, and energy metabolism in male dietinduced obese mice. [JOURNAL ARTICLE]
- Endocrinology 2014 Oct 16.:en20141604.
Effective and safe anti-obesity drugs are still needed in face of the obesity pandemic worldwide. Recent interventions in rodents revealed 3,5-diiodo-L-thyronine (3,5-T2) as a metabolically active iodothyronine affecting energy and lipid metabolism without thyromimetic side effects typically associated with 3,5,3'-triiodo-L-thyronine (T3) administration. Accordingly, 3,5-T2 has been proposed as a potential hypolipidemic agent for treatment of obesity and hepatic steatosis. In contrast to other observations, our experiments revealed dose-dependent thyromimetic effects of 3,5-T2 akin to those of T3 in diet-induced obese male C57BL/6J mice. 3,5-T2 treatment exerted a negative feedback regulation on the hypothalamus-pituitary-thyroid axis, similar to T3. This is demonstrated by decreased expression of genes responsive to thyroid hormones (TH) in pituitary resulting in a suppressed thyroid function with lower T4 and T3 concentrations in serum and liver of 3,5-T2 treated mice. Analyses of hepatic TH target genes involved in lipid metabolism revealed T3-like changes in gene expression and increased type I-deiodinase (Dio1) activity after application of 3,5-T2 (2.5 μ g/g body weight). Reduced hepatic triglyceride and serum cholesterol concentrations reflected enhanced lipid metabolism. Desired increased metabolic rate and reduction of different fat depots were, however, compromised by increased food intake preventing significant body weight loss. Moreover, enlarged heart weights indicate potential cardiac side effects of 3,5-T2 beyond hepatic thyromimetic actions. Altogether the observed thyromimetic effects of 3,5-T2 in several mouse TH target tissues raise concern about indiscriminate administration of 3,5-T2 as powerful natural hormone for the treatment of hyperlipidemia and pandemic obesity.
- Anti-Müllerian Hormone regulation by the Bone Morphogenetic Proteins in the sheep ovary: deciphering a direct regulatory pathway. [JOURNAL ARTICLE]
- Endocrinology 2014 Oct 16.:en20141551.
In the ovary, anti-Müllerian hormone (AMH) is produced by the granulosa cells of growing follicles and can modulate the recruitment of primordial follicles and the follicle stimulating hormone (FSH)-dependent development of follicles. However, the regulation of its production remains poorly understood. Recently, a stimulating effect of the bone morphogenetic proteins (BMPs) on AMH production by granulosa cells has been shown in vitro, but the molecular mechanisms implicated in this regulation and its physiological importance in ovarian function have not yet been established. In the hyperprolific Booroola ewes carrying the FecB(B) partial loss-of-function mutation in the gene encoding the FecB/BMPR1B receptor, the granulosa cells of antral follicles expressed and secreted low AMH amounts, resulting in low AMH concentrations in blood, despite high numbers of AMH-secreting follicles in ovaries. The presence of the FecB(B) mutation impaired the granulosa cell response to the stimulating action of BMP4 on AMH production, indicating a crucial role of the BMPR1B receptor in AMH regulation. In ovine granulosa cells, BMP4 enhanced the transcriptional activity of the human AMH promoter and this action depended on the presence of SMAD1, acting on a promoter sequence located between -423 and -202 bp upstream of the AMH transcription start site. SMAD1 and SF1 acted in concert to mediate BMP4 action on the AMH promoter. Among the two SF1 binding sites present on the AMH promoter, the most proximal site, located at -92 bp upstream of the AMH transcription start site, was found to be critical for ensuring the response of the AMH promoter to BMP4. In conclusion, AMH could mediate the actions of BMPs in regulating follicular development and contributing to the determination of ovulation numbers. A molecular model of regulation of the AMH promoter transactivation by BMP signaling is proposed.
- RF9 Excitation of GnRH Neurons Is Dependent Upon Kiss1r in the Adult Male and Female Mouse. [JOURNAL ARTICLE]
- Endocrinology 2014 Oct 16.:en20141517.
The neuropeptide FF receptor antagonist 1-adamantanecarbonyl-Arg-Phe-NH2 trifluoroacetate salt (RF9) has been found to be a remarkably potent activator of gonadotropin secretion in mammals. However, the mechanism of RF9 action on the reproductive axis is unknown. Using acute brain slice electrophysiology in genetically modified mouse models, we have investigated the possibility that RF9 may activate GnRH neurons. In transgenic GnRH-GFP male and female mice, RF9 was found to exert potent, dose-dependent, stimulatory effects on the firing rate of approximately 70 of GnRH neurons. These effects occurred directly on GnRH neurons and were independent of fast amino acid transmission. To assess RF9's action as an neuropeptide FF receptor antagonist at the GnRH neuron, its ability to antagonize the inhibitory effects of RFamide-related peptide-3 on GnRH neuron firing was examined. RF9 exhibited variable ability to prevent the inhibitory effects of RFamide-related peptide-3 on GnRH neurons. Whole-cell recordings from GnRH neurons showed that RF9 generated an inward current in GnRH neurons reminiscent of that evoked by kisspeptin. We therefore examined RF9 actions in kisspeptin receptor knockout mice. RF9 was found to have no effects at all on GnRH neurons in GnRH-GFP;Kiss1r-null mice, although these cells exhibited normal intrinsic electrical properties and remained responsive to GABA and glutamate. This study reveals that RF9 directly activates GnRH neurons in the mouse and that this is dependent upon Kiss1r expression.
- Ghrelin-related peptides exert protective effects in the cerebral circulation of male mice through a non-classical ghrelin receptor(s). [JOURNAL ARTICLE]
- Endocrinology 2014 Oct 16.:en20141415.
The ghrelin-related peptides, acylated ghrelin, des-acylated ghrelin, and obestatin, are novel gastrointestinal hormones. We firstly investigated whether the ghrelin gene, GOAT, and the ghrelin receptor (growth hormone secretagogue receptor 1a [GHSR1a]) are expressed in mouse cerebral arteries. Secondly, we assessed the cerebrovascular actions of ghrelin-related peptides by examining their effects on vasodilator nitric oxide (NO) and superoxide production. Using RT-PCR, we found the ghrelin gene and GOAT to be expressed at negligible levels in cerebral arteries from male wild-type mice. mRNA expression of GHSR1a was also found to be low in cerebral arteries, and GHSR protein was undetectable in GHSR-eGFP mice. We next found that exogenous acylated ghrelin had no effect on the tone of perfused cerebral arteries, or superoxide production. By contrast, exogenous des-acylated ghrelin or obestatin elicited powerful vasodilator responses (EC50 values <10 pmol/L) that were abolished by the NO synthase inhibitor L-NAME. Furthermore, exogenous des-acylated ghrelin suppressed superoxide production in cerebral arteries. Consistent with our GHSR expression data, vasodilator effects of des-acylated ghrelin or obestatin were sustained in the presence of YIL-781 (GHSR1a antagonist) and in arteries from Ghsr-deficient mice. Using ghrelin-deficient (Ghrl(-/-)) mice, we also found that endogenous production of ghrelin-related peptides regulates NO bioactivity and superoxide levels in the cerebral circulation. Specifically, we show that NO bioactivity was markedly reduced in Ghrl(-/-) versus WT mice, and superoxide levels were elevated. These findings reveal protective actions of exogenous and endogenous ghrelin-related peptides in the cerebral circulation, and show the existence of a novel ghrelin receptor(s) in the cerebral endothelium.