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Clinical, biochemical, and molecular overview of transaldolase deficiency and evaluation of the endocrine function: Update of 34 patients

Williams M, Valayannopoulos V, Altassan R, Chung WK, Heijboer AC, Keng WT, et al.

J Inherit Metab Dis, 2019 01;42(1):147-158.
PMID: 30740741 DOI: 10.1002/jimd.12036

BACKGROUND: Transaldolase deficiency (TALDO-D) is a rare autosomal recessive inborn error of the pentose phosphate pathway. Since its first description in 2001, several case reports have been published, but there has been no comprehensive overview of phenotype, genotype, and phenotype-genotype correlation.
METHODS: We performed a retrospective questionnaire and literature study of clinical, biochemical, and molecular data of 34 patients from 25 families with proven TALDO-D. In some patients, endocrine abnormalities have been found. To further evaluate these abnormalities, we performed biochemical investigations on blood of 14 patients.
RESULTS AND CONCLUSIONS: Most patients (n = 22) had an early-onset presentation (prenatally or before 1 month of age); 12 patients had a late-onset presentation (3 months to 9 years). Main presenting symptoms were intrauterine growth restriction, dysmorphic facial features, congenital heart disease, anemia, thrombocytopenia, and hepato(spleno)megaly. An older sib of two affected patients was asymptomatic until the age of 9 years, and only after molecular diagnosis was hepatomegaly noted. In some patients, there was gonadal dysfunction with low levels of testosterone and secondary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) abnormalities later in life. This overview provides information that can be helpful for managing patients and counseling families regarding prognosis. Diagnostic guidelines, possible genotype-phenotype correlations, treatment options, and pathophysiological disease mechanisms are proposed.

Matched MeSH terms: 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
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*
Fulltext Changes in Metabolic Hormones in Malaysian Young Adults following Helicobacter pylori Eradication

Yap TW, Leow AH, Azmi AN, Francois F, Perez-Perez GI, Blaser MJ, et al.

PLoS One, 2015;10(8):e0135771.
PMID: 26291794 DOI: 10.1371/journal.pone.0135771

More than half of the world's adults carry Helicobacter pylori. The eradication of H. pylori may affect the regulation of human metabolic hormones. The aim of this study was to evaluate the effect of H. pylori eradication on meal-associated changes in appetite-controlled insulinotropic and digestive hormones, and to assess post-eradication changes in body mass index as part of a currently on-going multicentre ESSAY (Eradication Study in Stable Adults/Youths) study.

Matched MeSH terms: Gastrointestinal Hormones/metabolism*
Effect of diisobutyl adipate on the expression of biomarker genes that respond to endocrine disruption and on gonadal sexual differentiation in Japanese medaka (Oryzias latipes)

Horie Y, Chihaya Y, Yap CK, Ríos JM, Ramaswamy BR, Uaciquete D

Comp Biochem Physiol C Toxicol Pharmacol, 2024 Mar;277:109836.
PMID: 38218565 DOI: 10.1016/j.cbpc.2024.109836

Phthalate and non-phthalate plasticizers are used in polymer materials, such as plastic and rubber. It has recently been found that diisobutyl adipate (DIBA), which is considered an environmentally safe non-phthalate plasticizer, potentially acts as a thyroid disruptor in fish. Here, we investigated the sexual hormone effects of DIBA based on the expression levels of genes that respond to endocrine disruption and sexual hormone activity in the livers and gonads, and on gonadal sexual differentiation in Japanese medaka. Compared with the control group, the mRNA expression of chgH, vtg1, vtg2, and esr1 was significantly suppressed in the livers of DIBA exposed XX individuals. Furthermore, the mRNA expression of gsdf was significantly upregulated and downregulated in the gonads of XX and XY individuals, respectively. The mRNA expressions of esr1 and esr2b were significantly suppressed by DIBA exposure in the gonads of both XX and XY individuals. These observations suggest that DIBA has potential androgenic activity in Japanese medaka. However, normal testes and ovaries were observed in respective XY and XX medaka after DIBA exposure; therefore, these results suggest that DIBA may have weak androgenic activity.

Matched MeSH terms: 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
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*
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
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
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*
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
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*
D-pinitol mitigates tumor growth by modulating interleukins and hormones and induces apoptosis in rat breast carcinogenesis through inhibition of NF-κB

Rengarajan T, Nandakumar N, Rajendran P, Ganesh MK, Balasubramanian MP, Nishigaki I

J Physiol Biochem, 2015 Jun;71(2):191-204.
PMID: 25827943 DOI: 10.1007/s13105-015-0397-9

Breast cancer is the most prevalent malignant neoplasm in the world, and chemoprevention through dietary intervention strategy is an emerging option to reduce the incidence. D-pinitol (DP), a major component of soya bean, possesses attractive biological actions. We have investigated whether D-pinitol have an effect on tumor growth in vivo against 7,12-dimethylbenz(a)anthracene (DMBA)-initiated rat mammary carcinogenesis and investigated its mechanism of action. Tumors were induced in Sprague-Dawley (SD) rats by a gastric dose of 20 mg/kg DMBA, and after 13 weeks of induction period, the rats were orally administered with D-pinitol for 45 days. At the end of the assay, animals in carcinogen control group prompted a tumor incidence of 100 % and developed a tumor volume of 8.35 ± 0.56, which was significantly reduced to 5.74 ± 0.32 for the animals treated with D-pinitol. The D-pinitol treatment not only decreased the tumor volume but also further examination revealed that tumors from animals that received D-pinitol reduced nuclear factor kappa B (NF-κB) activation which in turn results in modulation of its downstreaming p53 and proteins of caspase-3 family. Bcl-2 expression and caspase-3 activation were also decreased after D-pinitol supplementation leading to induction of apoptosis and finally cell death. Furthermore, the status of the inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-2, IL-6, and tumor markers, lipid profile, and hormones was also significantly declined up on D-pinitol administration. Thus, it reveals the collective involvement of the above-mentioned parameters along with NF-κB signaling through which D-pinitol induces apoptosis and subsequently suppresses breast cancer during DMBA-induced rat breast carcinogenesis.

Matched MeSH terms: Hormones/metabolism*
Fulltext Effects of a juvenile hormone analogue pyriproxyfen on monogynous and polygynous colonies of the Pharaoh ant Monomorium pharaonis (Hymenoptera: Formicidae)

Tay JW, Lee CY

Trop Biomed, 2015 Sep;32(3):453-62.
PMID: 26695205 MyJurnal

To evaluate the effects of the juvenile hormone analogue pyriproxyfen on colonies of the Pharaoh ant Monomorium pharaonis (L.), peanut oil containing different concentrations (0.3, 0.6, or 0.9%) of pyriproxyfen was fed to monogynous (1 queen, 500 workers, and 0.1 g of brood) and polygynous (8 queens, 50 workers, and 0.1 g of brood) laboratory colonies of M. pharaonis. Due to its delayed activity, pyriproxyfen at all concentrations resulted in colony elimination. Significant reductions in brood volume were recorded at weeks 3 - 6, and complete brood mortality was observed at week 8 in all treated colonies. Brood mortality was attributed to the disruption of brood development and cessation of egg production by queens. All polygynous colonies exhibited significant reduction in the number of queens present at week 10 compared to week 1. Number of workers was significantly lower in all treated colonies compared to control colonies at week 8 due to old-age attrition of the workers without replacement. At least 98.67 ± 1.33% of workers were dead at week 10 in all treated colonies. Thus, treatment with slow acting pyriproxyfen at concentrations of 0.3 - 0.9% is an effective strategy for eliminating Pharaoh ant colonies.

Matched MeSH terms: Juvenile Hormones/metabolism*
Expression of proteins related to thyroid hormone function in the uterus is down-regulated at the day of implantation in hypothyroid pregnant rats

Salleh N, Sayem ASM, Giribabu N, Khaing SL

Cell Biol Int, 2019 May;43(5):486-494.
PMID: 30761678 DOI: 10.1002/cbin.11114

Hypothyroidism has been linked to infertility, but the mechanisms underlying infertility-related hypothyroidism have yet to be fully elucidated. Therefore, in this study, effects of hypothyroidism on expression of the proteins related to thyroid hormone function in the uterus, which were thought to play a role implantation, including thyroid hormone receptor (TR), thyroid stimulating hormone receptor (TSHR), retinoic acid receptor (RAR) and extracellular kinase (ERK) were identified. Pregnant female rats were rendered hypothyroid by giving methimazole (MMI), orally. Following hypothyroid induction, rats were grouped into control (non-treated) and received subcutaneous thyroxine at 20, 40, and 80 μg/kg/day for five consecutive days. At Day 6, which is the day of implantation (GD 6), rats were sacrificed and the number of embryo implantation site in the uterus was calculated. Then, uterine horns were harvested and expression of the above proteins and their mRNAs were identified by Western blotting and real-time PCR, respectively. In non-treated hypothyroid pregnant rats, the number of embryo implantation sites decreased as compared to euthyroid and hypothyroid rats receiving thyroxine treatment. Similarly, expression of TRα-1, TRβ-1, TSHR, ERK1/2 and RAR proteins and mRNA in the uterus of non-treated hypothyroid rats also decreased (P

Matched MeSH terms: Thyroid Hormones/metabolism*
Comparative study of immunopathophysiological responses induced by B. melitensis and its lipopolysaccharide in mouse model infected via intranasal route of exposure

Osman AY, Saharee AA, Jesse FF, Kadir AA

Microb Pathog, 2017 Sep;110:365-374.
PMID: 28710016 DOI: 10.1016/j.micpath.2017.07.014

In this study, we developed a mouse model and characterized the effects of intranasal inoculation of virulent Brucella melitensis strain 16M and its lipopolysaccharide (LPS). The effects of the exposure were compared with respective control groups. Both Brucella melitensis-infected and LPS-infected groups showed no significant clinical presentation with minor relevance in the mortality associated with the infection. In Brucella melitensis-infected group, significant histopathological changes in comparison to the LPS infected group with increase bacterial burden in the lungs, reproductive and reticuloendothelial organs were observed. However, both infected groups showed elevated levels of pro-inflammatory cytokine expression (IL-1β and IL6) and antibody production (IgM an IgG) as early as 3 days post-infection with predominance in LPS infected group. In contrast, low levels of sex related hormonal changes was recorded in both infected groups throughout the experimental period. This is the first detailed investigation comparing the infection progression and host responses in relation to the immunopathophysiological aspects in mouse model after intranasal inoculation with B. melitensis and its lipopolysaccharide. The study revealed a significant difference between infected and control groups with overlap in clinical, pathological, and immunological responses as well as sex related hormonal changes resulting from the infections.

Matched MeSH terms: Gonadal Steroid Hormones/metabolism
Fulltext Effect of 11β-HSD1 dehydrogenase activity on bone histomorphometry of glucocorticoid-induced osteoporotic male Sprague-Dawley rats

Elvy Suhana MR, Farihah HS, Faizah O, Nazrun AS, Norazlina M, Norliza M, et al.

Singapore Med J, 2011 Nov;52(11):786-93.
PMID: 22173247

Glucocorticoids cause osteoporosis by decreasing bone formation and increasing bone resorption activity. Glucocorticoid action in bones depends on the activity of 11-beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme, which plays an important role in regulating corticosteroids. 11β-HSD1 is expressed by human and rat osteoblasts. We aimed to investigate the relationship between 11β-HSD1 dehydrogenase activity and bone histomorphometric changes in glucocorticoid-induced osteoporotic bone in rats.

Matched MeSH terms: Adrenal Cortex 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*
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

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