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Tumour biology of obesity-related cancers: understanding the molecular concept for better diagnosis and treatment

Teoh SL, Das S

Tumour Biol., 2016 Nov;37(11):14363-14380.
PMID: 27623943

Obesity continues to be a major global problem. Various cancers are related to obesity and proper understanding of their aetiology, especially their molecular tumour biology is important for early diagnosis and better treatment. Genes play an important role in the development of obesity. Few genes such as leptin, leptin receptor encoded by the db (diabetes), pro-opiomelanocortin, AgRP and NPY and melanocortin-4 receptors and insulin-induced gene 2 were linked to obesity. MicroRNAs control gene expression via mRNA degradation and protein translation inhibition and influence cell differentiation, cell growth and cell death. Overexpression of miR-143 inhibits tumour growth by suppressing B cell lymphoma 2, extracellular signal-regulated kinase-5 activities and KRAS oncogene. Cancers of the breast, uterus, renal, thyroid and liver are also related to obesity. Any disturbance in the production of sex hormones and insulin, leads to distortion in the balance between cell proliferation, differentiation and apoptosis. The possible mechanism linking obesity to cancer involves alteration in the level of adipokines and sex hormones. These mediators act as biomarkers for cancer progression and act as targets for cancer therapy and prevention. Interestingly, many anti-cancerous drugs are also beneficial in treating obesity and vice versa. We also reviewed the possible link in the mechanism of few drugs which act both on cancer and obesity. The present review may be important for molecular biologists, oncologists and clinicians treating cancers and also pave the way for better therapeutic options.

Matched MeSH terms: Gonadal Steroid Hormones/metabolism
Thyroid hormones: Possible roles in epilepsy pathology

Tamijani SM, Karimi B, Amini E, Golpich M, Dargahi L, Ali RA, et al.

Seizure, 2015 Sep;31:155-64.
PMID: 26362394 DOI: 10.1016/j.seizure.2015.07.021

Thyroid hormones (THs) L-thyroxine and L-triiodothyronine, primarily known as metabolism regulators, are tyrosine-derived hormones produced by the thyroid gland. They play an essential role in normal central nervous system development and physiological function. By binding to nuclear receptors and modulating gene expression, THs influence neuronal migration, differentiation, myelination, synaptogenesis and neurogenesis in developing and adult brains. Any uncorrected THs supply deficiency in early life may result in irreversible neurological and motor deficits. The development and function of GABAergic neurons as well as glutamatergic transmission are also affected by THs. Though the underlying molecular mechanisms still remain unknown, the effects of THs on inhibitory and excitatory neurons may affect brain seizure activity. The enduring predisposition of the brain to generate epileptic seizures leads to a complex chronic brain disorder known as epilepsy. Pathologically, epilepsy may be accompanied by mitochondrial dysfunction, oxidative stress and eventually dysregulation of excitatory glutamatergic and inhibitory GABAergic neurotransmission. Based on the latest evidence on the association between THs and epilepsy, we hypothesize that THs abnormalities may contribute to the pathogenesis of epilepsy. We also review gender differences and the presumed underlying mechanisms through which TH abnormalities may affect epilepsy here.

Matched MeSH terms: Thyroid Hormones/metabolism*
Fulltext The Role of GnIH in Biological Rhythms and Social Behaviors

Teo CH, Phon B, Parhar I

Front Endocrinol (Lausanne), 2021;12:728862.
PMID: 34566893 DOI: 10.3389/fendo.2021.728862

Gonadotropin-inhibitory hormone (GnIH) was first discovered in the Japanese quail, and peptides with a C-terminal LPXRFamide sequence, the signature protein structure defining GnIH orthologs, are well conserved across vertebrate species, including fish, reptiles, amphibians, avians, and mammals. In the mammalian brain, three RFamide-related proteins (RFRP-1, RFRP-2, RFRP-3 = GnIH) have been identified as orthologs to the avian GnIH. GnIH is found primarily in the hypothalamus of all vertebrate species, while its receptors are distributed throughout the brain including the hypothalamus and the pituitary. The primary role of GnIH as an inhibitor of gonadotropin-releasing hormone (GnRH) and pituitary gonadotropin release is well conserved in mammalian and non-mammalian species. Circadian rhythmicity of GnIH, regulated by light and seasons, can influence reproductive activity, mating behavior, aggressive behavior, and feeding behavior. There is a potential link between circadian rhythms of GnIH, anxiety-like behavior, sleep, stress, and infertility. Therefore, in this review, we highlight the functions of GnIH in biological rhythms, social behaviors, and reproductive and non-reproductive activities across a variety of mammalian and non-mammalian vertebrate species.

Matched MeSH terms: Hypothalamic Hormones/metabolism*
The Functional Significance of Endocrine-immune Interactions in Health and Disease

Muthusami S, Vidya B, Shankar EM, Vadivelu J, Ramachandran I, Stanley JA, et al.

Curr Protein Pept Sci, 2020;21(1):52-65.
PMID: 31702489 DOI: 10.2174/1389203720666191106113435

Hormones are known to influence various body systems that include skeletal, cardiac, digestive, excretory, and immune systems. Emerging investigations suggest the key role played by secretions of endocrine glands in immune cell differentiation, proliferation, activation, and memory attributes of the immune system. The link between steroid hormones such as glucocorticoids and inflammation is widely known. However, the role of peptide hormones and amino acid derivatives such as growth and thyroid hormones, prolactin, dopamine, and thymopoietin in regulating the functioning of the immune system remains unclear. Here, we reviewed the findings pertinent to the functional role of hormone-immune interactions in health and disease and proposed perspective directions for translational research in the field.

Matched MeSH terms: Thyroid Hormones/metabolism
The Bio-Psycho-Social Dimension in Women's Sexual Desire: 'Argumentum ad novitatem'

Roslan NS, Jaafar NRN, Sidi H, Baharudin N, Kumar J, Das S, et al.

Curr Drug Targets, 2019;20(2):146-157.
PMID: 28641524 DOI: 10.2174/1389450118666170622090337

Sexual desire includes complex motivation and drive. In the context of biological and cognitive- emotive state art of science, it is often a neglected field in medicine. In regard to the treatment, study on women's sexual function received less attention compared to the men's sexuality. In the past, this endeavor was relatively not well disseminated in the scientific community. Recently, there was a revolutionized surge of drug targets available to treat women with low sexual desire. It is timely to review the relevant biological approach, especially in the context of pharmacotherapy to understand this interesting clinical entity which was modulated by numerous interactive psychosocial inter-play and factors. The complex inter-play between numerous dimensional factors lends insights to understand the neural mechanism, i.e. the rewards centre pathway and its interaction with external psychosocialstimulus, e.g. relationship or other meaningful life events. The function of hormones, e.g. oxytocin or testosterone regulation was described. The role of neurotransmitters as reflected by the introduction of a molecule of flibenserin, a full agonist of the 5-HT1A and partial agonist of the D4 to treat premenopausal women with low sexual desire was deliberated. Based on this fundamental scientific core knowledge, we suggest an outline on know-how of introduction for sex therapy (i.e. "inner-self" and "outer-self") where the role of partner is narrated. Then, we also highlighted on the use of pharmacological agent as an adjunct scope of therapy, i.e. phosphodiasterase-5 (PDE-5) inhibitors and hormonal treatment in helping the patient with low sexual desire.

Matched MeSH terms: Hormones/metabolism*
Fulltext Testosterone Reduces Tight Junction Complexity and Down-regulates Expression of Claudin-4 and Occludin in the Endometrium in Ovariectomized, Sex-steroid Replacement Rats

Mokhtar MH, Giribabu N, Salleh N

In Vivo, 2019 12 29;34(1):225-231.
PMID: 31882482 DOI: 10.21873/invivo.11764

BACKGROUND/AIM: It was hypothesized that endometrial tight junction morphology and expression of tight junction proteins i.e., claudin-4 and occludin in the uterus, are affected by testosterone. Therefore, the effects of testosterone on these parameters in the uterus during receptivity period were investigated.
MATERIALS AND METHODS: Ovariectomized adult female rats were given testosterone (1 mg/kg/day) alone or in combination with flutamide or finasteride between days 6 to 8 of sex-steroid replacement treatment, which was considered the period of uterine receptivity. Ultramorphology of tight junctions was visualized by transmission electron microscopy while distribution and expression of claudin-4 and occludin were examined by immunofluorescence and real-time polymerase chain reaction respectively.
RESULTS: Administration of testosterone caused loss of tight junction complexity and down-regulated expression of claudin-4 and occludin in the uterus.
CONCLUSION: Decreased endometrial tight junction complexity and expression of claudin-4 and occludin in the uterus during receptivity period by testosterone may interfere with embryo attachment and subsequent implantation.

Matched MeSH terms: Gonadal Steroid Hormones/metabolism
Steroid profiling in the study of rat testicular steroidogenesis

Kwan TK, Pertiwi AK, Taylor NF, Gower DB

Biochim. Biophys. Acta, 1988 Sep 23;962(2):214-9.
PMID: 3167079

Twenty authentic steroids, derivatized as O-methyl oximes (MO), trimethylsilyl (TMS) ethers or as MO-TMS ethers have been subjected to capillary gas chromatography using two different columns. Virtually all of the steroid derivatives have been resolved, one difficult pair to separate being 5,16-androstadien-3 beta-ol and 5 alpha-androst-16-en-3 beta-ol on the non-selective phase OV-1. Where syn and anti forms of MO derivatives arose, these were also resolved under the conditions utilised. This technique of 'steroid profiling' has been applied to the separation and quantification of metabolites of pregnenolone which were formed during incubations of the microsomal and cytosolic fractions from rat testes. The majority of the metabolites were found in the microsomal incubation. These compounds included some odorous 16-androstenes as well as other C21 and C19 steroids, the formation of which was consistent with the 5-ene and 4-ene pathways of testosterone biosynthesis being operative. In addition, evidence was obtained for 16 alpha-hydroxylation of C21 steroids. Very much less metabolic activity was found in the cytosolic fraction of rat testes. Metabolic pathways have been proposed which both confirm and extend earlier work. We conclude that the rat testis can only form some of the odorous, possibly pheromonal, 16-androstenes and that these are quantitatively less important than in the porcine testis.

Matched MeSH terms: Gonadal Steroid Hormones/metabolism
Standardized quassinoid-rich Eurycoma longifolia extract improved spermatogenesis and fertility in male rats via the hypothalamic-pituitary-gonadal axis

Low BS, Das PK, Chan KL

J Ethnopharmacol, 2013 Feb 13;145(3):706-14.
PMID: 23261482 DOI: 10.1016/j.jep.2012.11.013

Eurycoma longifolia Jack, a small Simaroubaceae tree, known locally as 'Tongkat Ali' is popularly used as a sexual tonic in traditional medicine for aphrodisiac activity and improvement of fertility and male libido.

Matched MeSH terms: Hormones/metabolism
Fulltext Single-Cell Gene Profiling Reveals Social Status-Dependent Modulation of Nuclear Hormone Receptors in GnRH Neurons in a Male Cichlid Fish

Ogawa S, Parhar IS

Int J Mol Sci, 2020 Apr 15;21(8).
PMID: 32326396 DOI: 10.3390/ijms21082724

Gonadotropin-releasing hormone (GnRH) is essential for the initiation and maintenance of reproductive functions in vertebrates. To date, three distinct paralogue lineages, GnRH1, GnRH2, and GnRH3, have been identified with different functions and regulatory mechanisms. Among them, hypothalamic GnRH1 neurons are classically known as the hypophysiotropic form that is regulated by estrogen feedback. However, the mechanism of action underlying the estrogen-dependent regulation of GnRH1 has been debated, mainly due to the coexpression of low levels of estrogen receptor (ER) genes. In addition, the role of sex steroids in the modulation of GnRH2 and GnRH3 neurons has not been fully elucidated. Using single-cell real-time PCR, we revealed the expression of genes for estrogen, androgen, glucocorticoid, thyroid, and xenobiotic receptors in GnRH1, GnRH2, and GnRH3 neurons in the male Nile tilapia Oreochromis niloticus. We further quantified expression levels of estrogen receptor genes (ERα, ERβ, and ERγ) in three GnRH neuron types in male tilapia of two different social statuses (dominant and subordinate) at the single cell level. In dominant males, GnRH1 mRNA levels were positively proportional to ERγ mRNA levels, while in subordinate males, GnRH2 mRNA levels were positively proportional to ERβ mRNA levels. These results indicate that variations in the expression of nuclear receptors (and possibly steroid sensitivities) among individual GnRH cells may facilitate different physiological processes, such as the promotion of reproductive activities through GnRH1 neurons, and the inhibition of feeding and sexual behaviors through GnRH2 neurons.

Matched MeSH terms: Thyroid Hormones/metabolism
Sexual maturation modulates expression of nuclear receptor types in laser-captured single cells of the cichlid (Oreochromis niloticus) pituitary

Kitahashi T, Ogawa S, Soga T, Sakuma Y, Parhar I

Endocrinology, 2007 Dec;148(12):5822-30.
PMID: 17823257

The role of steroid/thyroid hormones in the regulation of endocrine cells at the level of the pituitary has remained unclear. Therefore, using single-cell quantitative real-time PCR, we examined absolute amounts of transcripts for nuclear receptors [estrogen receptors (ERs) alpha, beta, and gamma; androgen receptors (ARs) a and b; glucocorticoid receptors (GRs) 1, 2a, and 2b; and thyroid hormone receptors (TRs) alpha1, alpha2, and beta] in pituitary cells of immature (IM) and mature (M) male tilapia, Oreochromis niloticus. In the two reproductive stages, ACTH cells expressed only ERbeta, whereas all other pituitary cell types expressed ERalpha + beta, and a subpopulation coexpressed ARa, ARb, GR1, GR2b, and TRbeta but lacked ERgamma, GR2a, TRalpha1, and TRalpha2. IM males had high percentages of LH cells (IM 46.0% vs. M 10.0%), GH cells (IM 23.3% vs. M 7.9%), and prolactin cells (IM 68.8% vs. M 6.0%) with ERbeta, and TSH cells (IM 19.2% vs. M 0.0%) and MSH cells (IM 25.6% vs. M 0.0%) with ERalpha + TRbeta. A high percentage of FSH cells in IM males expressed ERbeta (IM 46.9% vs. M 18.8%), and FSH cells in M males showed significantly high GR1 transcripts (IM 76.0 +/- 5.0 vs. M 195.0 +/- 10.7 copies per cell; P < 0.05), suggesting that FSH cells are regulated differently in the two reproductive stages. Coexpression of ERalpha + beta in high percentages of cells of the GH family (GH, IM 43.8% vs. M 14.3%; prolactin, IM 8.3% vs. M 59.7%; somatolactin, IM 22.2% vs. M 42.2%) suggests that the expression of both ERs is important for functionality. Thus, differential coexpression of genes for nuclear receptors in subpopulations of pituitary cell types suggests multiple steroid/thyroid hormone regulatory pathways at the level of the pituitary during the two reproductive stages.

Matched MeSH terms: Pituitary Hormones/metabolism
Reproductive immunomodulatory functions of B cells in pregnancy

Dutta S, Sengupta P, Haque N

Int Rev Immunol, 2020;39(2):53-66.
PMID: 31608717 DOI: 10.1080/08830185.2019.1674299

Pregnancy, a challenging physiological state, requires shuffling of conventional immune work-sets. Strategies to tolerate the semi-allogenic fetus in normal human pregnancy are multivariate with perfect modulation of the immune cells. Pregnancy is marked by B cell lymphocytopenia accompanied by reduced responsiveness to infectious agents. Besides this old age concept, plenty of research confirms that B cells have other crucial roles in pregnancy and undergo a wide range of modifications in terms of its proliferation, switching between its subtypes, variation in antibody productions, shifting the tides of cytokines as well as regulating other immune cells. B cells establish tolerant environment in pregnancy by producing protective antibodies to encounter the foreign paternal antigens. Regulatory B cells (Bregs) have adopted anti-inflammatory characteristics to sustain normal pregnancy. Moreover, the colossal physiological alterations during human pregnancy also include synchronized changes in the cross-talks between the pregnancy hormones and B cells. These aspects of pregnancy from the view point of B cell functions have so far appeared individually in discrete reports. This review finds its novelty in concisely presenting every facet of association of B cell with human pregnancy.

Matched MeSH terms: Gonadal Steroid Hormones/metabolism
Protective role of pectin against cadmium-induced testicular toxicity and oxidative stress in rats

Koriem KM, Fathi GE, Salem HA, Akram NH, Gamil SA

Toxicol. Mech. Methods, 2013 May;23(4):263-72.
PMID: 23193971 DOI: 10.3109/15376516.2012.748857

Cadmium has been classified as an environmental pollutant and human carcinogen. Pectin is a family of complex polysaccharides that function as hydrating agents and cementing materials for the cellulosic network. The aim of this study was to evaluate the protective role of pectin against cadmium-induced testicular toxicity and oxidative stress in rats. Forty male Wistar rats were divided into five equal groups. Groups 1 and 2 were injected intraperitoneally (i.p.) saline (1 mg/kg) and pectin (50 mg/kg), respectively, two days/weeks over three weeks period. Groups 3-5 were injected i.p. with 1 mg/kg cadmium two days/week while groups 4 and 5 co-administrated i.p. with 25 and 50 mg/kg pectin, respectively, three days/week over three weeks period. The results of the present work revealed that cadmium-exposed rats showed decrease in serum testosterone, dehydroepiandrosterone sulfate and lactate dehydrogenase. Testicular cholesterol, total protein, glucose-6-phosphate dehydrogenase, 3β-hydroxysteroid dehydrogenase, superoxide dismutase, glutathione peroxidase, catalase, glutathione S-transferase and reduced glutathione levels were also decreased while testicular malondialdehyde level was increased after cadmium injection. On the other hand, serum luteinizing hormone, follicle stimulating hormone, sex hormone binding globulin and γ-glutamyl transpeptidase were increased after cadmium exposure. Cadmium also induced sperms loss. Co-administration of pectin with cadmium restores all the above parameters and sperms to the normal levels where pectin at higher dose was more effective than lower one. These results were supported by histochemical investigations. In conclusion, pectin can counteract the testicular toxicity and oxidative stress induced by cadmium and the effect was dose-dependent.

Matched MeSH terms: Gonadal Steroid Hormones/metabolism
Pregnenolone metabolites in rat testis: endogenous concentrations, and intracellular distribution in whole testes during incubation in vitro

Pertiwi AK, Kwan TK, Gower DB

J Steroid Biochem Mol Biol, 2002 Aug;81(4-5):363-7.
PMID: 12361726

The intracellular movements of pregnenolone in rat testes were investigated. Whole testes were incubated in the presence or absence of pregnenolone (2.5mM) in the medium for 120 min (in some studies 30, 60, and 90 min). The testes were homogenised, subcellular fractions prepared and analysed in quadruplicate for steroid content by gas chromatography-mass spectrometry with selected ion monitoring. Quantification of pregnenolone and 11 of its metabolites, obtained from non-incubated whole testes, provided values for endogenous amounts. Pregnenolone was the only steroid of quantitative importance found initially in the mitochondrial fraction but was subsequently found in the microsomal fraction, where metabolism occurred. Identification and quantification of metabolites indicated that both classical pathways for testosterone production were operating, with the 4-en-3-oxosteroid pathway predominating. By 120 min, virtually all pregnenolone metabolites, including pregnenolone itself, were found in the cytosol, consistent with an overall movement from mitochondria to endoplasmic reticulum to cytosol.

Matched MeSH terms: Gonadal Steroid Hormones/metabolism
Fulltext Oligosaccharides might contribute to the antidiabetic effect of honey: a review of the literature

Erejuwa OO, Sulaiman SA, Wahab MS

Molecules, 2011 Dec 28;17(1):248-66.
PMID: 22205091 DOI: 10.3390/molecules17010248

Evidence shows that honey improves glycemic control in diabetes mellitus. Besides its hypoglycemic effect, studies indicate that honey ameliorates lipid abnormalities in rats and humans with diabetes. The majority of these studies do not examine the mechanisms by which honey ameliorates glycemic and/or lipid derangements. The gut microbiota is now recognized for its ability to increase energy harvest from the diet and alter lipid metabolism of the host. Recently available data implicate a causal role of these gut microbes in the pathophysiology of obesity, insulin resistance, and diabetes mellitus. In this review, we present some of the latest findings linking gut microbiota to pathogenesis of obesity, insulin resistance, and diabetes mellitus. The review also underlines data that demonstrate the beneficial effects of oligosaccharides on various abnormalities commonly associated with these disorders. Based on the similarities of some of these findings with those of honey, together with the evidence that honey contains oligosaccharides, we hypothesize that oligosaccharides present in honey might contribute to the antidiabetic and other health-related beneficial effects of honey. We anticipate that the possibility of oligosaccharides in honey contributing to the antidiabetic and other health-related effects of honey will stimulate a renewed research interest in this field.

Matched MeSH terms: Pancreatic Hormones/metabolism
Molecular, cellular, morphological, physiological and behavioral aspects of gonadotropin-inhibitory hormone

Ubuka T, Son YL, Tsutsui K

Gen Comp Endocrinol, 2016 Feb 1;227:27-50.
PMID: 26409890 DOI: 10.1016/j.ygcen.2015.09.009

Gonadotropin-inhibitory hormone (GnIH) is a hypothalamic neuropeptide that was isolated from the brains of Japanese quail in 2000, which inhibited luteinizing hormone release from the anterior pituitary gland. Here, we summarize the following fifteen years of researches that investigated on the mechanism of GnIH actions at molecular, cellular, morphological, physiological, and behavioral levels. The unique molecular structure of GnIH peptide is in its LPXRFamide (X=L or Q) motif at its C-terminal. The primary receptor for GnIH is GPR147. The cell signaling pathway triggered by GnIH is initiated by inhibiting adenylate cyclase and decreasing cAMP production in the target cell. GnIH neurons regulate not only gonadotropin synthesis and release in the pituitary, but also regulate various neurons in the brain, such as GnRH1, GnRH2, dopamine, POMC, NPY, orexin, MCH, CRH, oxytocin, and kisspeptin neurons. GnIH and GPR147 are also expressed in gonads and they may regulate steroidogenesis and germ cell maturation in an autocrine/paracrine manner. GnIH regulates reproductive development and activity. In female mammals, GnIH may regulate estrous or menstrual cycle. GnIH is also involved in the regulation of seasonal reproduction, but GnIH may finely tune reproductive activities in the breeding seasons. It is involved in stress responses not only in the brain but also in gonads. GnIH may inhibit male socio-sexual behavior by stimulating the activity of cytochrome P450 aromatase in the brain and stimulates feeding behavior by modulating the activities of hypothalamic and central amygdala neurons.

Matched MeSH terms: Hypothalamic Hormones/metabolism*
Fulltext In vitro evaluation of Pandanus amaryllifolius ethanol extract for induction of cell death on non-hormone dependent human breast adenocarcinoma MDA-MB-231 cell via apoptosis

Chong HZ, Yeap SK, Rahmat A, Akim AM, Alitheen NB, Othman F, et al.

BMC Complement Altern Med, 2012;12:134.
PMID: 22909149 DOI: 10.1186/1472-6882-12-134

Our previous study had shown that P. amaryllifolius was able to selectively inhibit cell proliferation of hormone independent breast cancer cell line MDA-MB-231. To understand the mode of killing and mechanism of action for P. amaryllifolius, the ethanol extract was evaluated for their alteration of cell cycle progression, PS externalization, DNA fragmentation and expression of anti/pro-apoptotic related protein.

Matched MeSH terms: Hormones/metabolism
Fulltext In vitro cytotoxicity of Strobilanthes crispus ethanol extract on hormone dependent human breast adenocarcinoma MCF-7 cell

Chong HZ, Rahmat A, Yeap SK, Md Akim A, Alitheen NB, Othman F, et al.

BMC Complement Altern Med, 2012;12:35.
PMID: 22471785 DOI: 10.1186/1472-6882-12-35

Strobilanthes crispus has been traditionally used as antidiabetic, anticancer, diuretic, antilytic and laxative agent. However, cytotoxicity and antiproliferative effect of S. crispus is still unclear.

Matched MeSH terms: Hormones/metabolism
Fulltext Helicobacter pylori infection can affect energy modulating hormones and body weight in germ free mice

Khosravi Y, Seow SW, Amoyo AA, Chiow KH, Tan TL, Wong WY, et al.

Sci Rep, 2015;5:8731.
PMID: 25736205 DOI: 10.1038/srep08731

Helicobacter pylori, is an invariably commensal resident of the gut microbiome associated with gastric ulcer in adults. In addition, these patients also suffered from a low grade inflammation that activates the immune system and thus increased shunting of energy to host defense mechanisms. To assess whether a H. pylori infection could affect growth in early life, we determined the expression levels of selected metabolic gut hormones in germ free (GF) and specific pathogen-free (SPF) mice with and without the presence of H. pylori. Despite H. pylori-infected (SPFH) mice display alteration in host metabolism (elevated levels of leptin, insulin and peptide YY) compared to non-infected SPF mice, their growth curves remained the same. SPFH mice also displayed increased level of eotaxin-1. Interestingly, GF mice infected with H. pylori (GFH) also displayed increased levels of ghrelin and PYY. However, in contrast to SPFH mice, GFH showed reduced weight gain and malnutrition. These preliminary findings show that exposure to H. pylori alters host metabolism early in life; but the commensal microbiota in SPF mice can attenuate the growth retarding effect from H. pylori observed in GF mice. Further investigations of possible additional side effects of H. pylori are highly warranted.

Matched MeSH terms: Peptide Hormones/metabolism*
Gonadotropin-inhibitory hormone promoter-driven enhanced green fluorescent protein expression decreases during aging in female rats

Soga T, Kitahashi T, Clarke IJ, Parhar IS

Endocrinology, 2014 May;155(5):1944-55.
PMID: 24605826 DOI: 10.1210/en.2013-1786

Gonadotropin-inhibitory hormone (GnIH) neurons project to GnRH neurons to negatively regulate reproductive function. To fully explore the projections of the GnIH neurons, we created transgenic rats carrying an enhanced green fluorescent protein (EGFP) tagged to the GnIH promoter. With these animals, we show that EGFP-GnIH neurons are localized mainly in the dorsomedial hypothalamic nucleus (DMN) and project to the hypothalamus, telencephalon, and diencephalic thalamus, which parallels and confirms immunocytochemical and gene expression studies. We observed an age-related reduction in c-Fos-positive GnIH cell numbers in female rats. Furthermore, GnIH fiber appositions to GnRH neurons in the preoptic area were lessened in middle-aged females (70 weeks old) compared with their younger counterparts (9-12 weeks old). The fiber density in other brain areas was also reduced in middle-aged female rats. The expression of estrogen and progesterone receptors mRNA in subsets of EGFP-GnIH neurons was shown in laser-dissected single EGFP-GnIH neurons. We then examined estradiol-17β and progesterone regulation of GnIH neurons, using c-Fos presence as a marker. Estradiol-17β treatment reduced c-Fos labeling in EGFP-GnIH neurons in the DMN of young ovariectomized adult females but had no effect in middle-aged females. Progesterone had no effect on the number of GnIH cells positive for c-Fos. We conclude that there is an age-related decline in GnIH neuron number and GnIH inputs to GnRH neurons. We also conclude that the response of GnIH neurons to estrogen diminishes with reproductive aging.

Matched MeSH terms: Hypothalamic Hormones/metabolism*
Gonadotropin-inhibitory hormone mediates behavioral stress responses

Ubuka T, Parhar IS, Tsutsui K

Gen Comp Endocrinol, 2018 09 01;265:202-206.
PMID: 29510150 DOI: 10.1016/j.ygcen.2018.03.004

Gonadotropin-inhibitory hormone (GnIH) is an inhibitor of the hypothalamic-pituitary-gonadal (HPG) axis. GnIH is also called RFamide-related peptide (RFRP) as GnIH peptides have a characteristic C-terminal LPXRFiamide (X = L or Q) sequence. GnIH is thought to be the mediator of stress by negatively regulating the HPG axis as various stressors increase GnIH mRNA, GnIH peptide or GnIH neuronal activity. On the other hand, GnIH may also mediate behavioral stress responses as GnIH neuronal fibers and GnIH receptors are widely located in the limbic system of telencephalon, diencephalon and midbrain area. Previous studies have shown that intracerebroventricular (i.c.v.) administration of GnIH (RFRP) blocks morphine-induced analgesia in hot plate and formalin injection tests in rats suggesting that GnIH increases sensitivity to pain. GnIH (RFRP) also increases anxiety-like behavior in rats. RNA interference of GnIH gene (GnIH RNAi) increases locomotor activity of white-crowned sparrow and Japanese quail and i.c.v. administration of GnIH decreases GnIH RNAi induced locomotor activity. It was further shown that i.c.v. administration of GnIH (RFRP) decreases aggressive behavior in male quail and sexual behavior in male rats, female white-crowned sparrow and female hamsters. These results suggest that GnIH decreases threat to homeostasis of the organism by increasing pain sensitivity, anxiety and decreasing locomotor activity, aggressive behavior and sexual behavior. GnIH may also mediate the effect of stress on behavior.

Matched MeSH terms: Hypothalamic Hormones/metabolism

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