Endocrinology

Reducing ghrelin by ghrelin gene knockout (GKO), ghrelin-cell ablation, or high-fat diet feeding increases islet size and β-cell mass in male mice. Here, we determined if reducing ghrelin also enlarges islets in females, and if pregnancy-associated changes in islet size are related to reduced ghrelin. Islet size and β-cell mass were larger (P=0.057 for β-cell mass) in female GKO mice. Pregnancy was associated with reduced ghrelin and increased LEAP2 [a ghrelin receptor (GHSR) antagonist] in WT mice...

Clomiphene citrate is a common treatment for ovulation induction in subfertile women, but its use is associated with elevated risk of adverse perinatal outcomes and birth defects. To investigate the biological plausibility of a causal relationship, this study investigated in mice the consequences for fetal development and pregnancy outcome of peri-conception clomiphene citrate administration at doses approximating human exposures. A dose-dependent adverse effect of clomiphene citrate given twice in the 36 h after mating was seen, with a moderate dose of 0...

We examined the impact of the puberty blocker, leuprolide acetate, on sex differences in juvenile rough-and-tumble play behavior and anxiety-like behavior in adolescent male and female rats. We also evaluated leuprolide treatment on gonadal and pituitary hormone levels and activity-regulated cytoskeleton-protein mRNA levels within the adolescent amygdala, a region important for both rough-and-tumble play and anxiety-like behavior. Our findings suggest that leuprolide treatment lowered anxiety-like behavior during adolescent development, suggesting that the maturation of GnRH systems may be linked to increased anxiety...

In the classical insulin target tissues liver, muscle and adipose tissue, chronically elevated levels of free fatty acids (FFA) impair insulin signaling. Insulin signaling molecules are also present in β-cells where they play a role in β-cell function. Therefore, inhibition of the insulin/IGF-1 pathway may be involved in fat-induced β-cell dysfunction. To address the role of β-cell insulin resistance in FFA-induced β-cell dysfunction we co-infused bisperoxovanadate (BPV) with oleate or olive oil for 48 h in rats...

OBJECTIVE: Growth Factor Receptor Bound Protein 7 (GRB7) is a multi-domain signaling adaptor. Members of the Grb7/10/14 family, specifically Gbrb10/14, have important roles in metabolism. We ablated the Grb7 gene in mice to examine its metabolic function. METHODS: Global ablation of Grb7 in FVB/NJ mice was generated. Growth, organ weight, food intake, and glucose homeostasis were measured. Insulin signaling was examined by Western blotting. Fat and lean body mass was measured by Nuclear Magnetic Resonance, and body composition after fasting or high fat diet was assessed...

Klotho plays a critical role in the regulation of ion and fluid homeostasis. A previous study reported that haplo-insufficiency of Klotho in mice results in increased aldosterone synthase (CYP11B2) expression, elevated plasma aldosterone and high blood pressure. This phenotype was presumed to be the result of diminished Klotho expression in zona glomerulosa (zG) cells of the adrenal cortex, however systemic effects on adrenal aldosterone production could not be ruled out. To examine whether Klotho expressed in the zG is indeed a critical regulator of aldosterone synthesis, we generated a tamoxifen-inducible, zG-specific mouse model of Klotho deficiency by crossing Klotho-flox mice with Cyp11b2-CreERT mice (zG-Kl-KO)...

NAD+ is one of the most important metabolites for cellular activities, and its biosynthesis mainly occurs through the salvage pathway using the NAMPT enzyme. The main NAD consumers, PARP and SIRT enzymes, are heavily involved in DNA repair and chromatin remodeling. Since cancer cells shift their energy production pathway, NAD levels are significantly affected. NAD's roles in cell survival led to the use of NAD depletion in cancer therapies. NAMPT inhibition (alone or in combination with other cancer therapies, including endocrine therapy and chemotherapy) results in decreased cell viability and tumor burden for many cancer types...

Biological sex is a primary determinant of athletic human performance involving strength, power, speed, and aerobic endurance and is more predictive of athletic performance than gender. This perspective article highlights three key medical and physiological insights related to recent evolving research into the sex differences in human physical performance: (1) sex and gender are not the same; (2) males and females exhibit profound differences in physical performance with males outperforming females in events and sports involving strength, power, speed and aerobic endurance; (3) endogenous testosterone underpins sex differences in human physical performance with questions remaining on the roles of minipuberty in the sex differences in performance in prepubescent youth and the presence of the Y chromosome (SRY gene expression) in males, on athletic performance across all ages...

Fat (FAT atypical cadherin) and Dchs (Dachsous cadherin-related protein) in adjacent Sertoli:Sertoli, Sertoli:spermatid, and spermatid:spermatid create an important intercellular bridge, whose adhesive function is in turn supported by Fjx1, a non-receptor Ser/Thr protein kinase. This concept is derived from earlier studies of Drosophila, which has been confirmed in this and earlier reports as well. Herein, we use the approach of knockdown of Fat1 by RNAi using primary cultures of Sertoli cells that mimicked the blood-testis barrier (BTB) in vivo, and a series of coherent experiments including functional assays to monitor Sertoli cell tight junction (TJ)-permeability barrier and a functional in vitro TJ integrity assay to assess the role of Fat1 in the testis...

Lobular carcinoma represent the most common special histological subtype of breast cancer, with the majority classed as hormone receptor-positive. Rates of invasive lobular carcinoma (ILC) in postmenopausal women have been seen to increase globally, whilst other hormone receptor-positive breast cancers proportionally have not followed the same trend. This has been linked to exposure to exogenous ovarian hormones such as hormone replacement therapy (HRT). Reproductive factors resulting in increased lifetime exposure to endogenous ovarian hormones have also been linked to an increased risk of lobular breast cancer, and taken together, these data make a case for the role of ovarian hormones in the genesis and progression of the disease...

Thyroid hormones (THs), thyroxine (T4) and triiodothyronine (T3), are vital for development, growth, and metabolism. Thyroid dysfunction can also cause problems in fertility, suggesting involvement of THs in reproduction. In zebrafish, there exist two forms of TH receptor alpha gene (THRα: thraa and thrab). Disruption of these genes by CRISPR/Cas9 showed no reproductive irregularities in thraa mutant; however, inactivation of thrab gene resulted in female infertility. Although young female mutants (thrabm/m) showed normal ovarian development and folliculogenesis before sexual maturation, they failed to release eggs during oviposition after sexual maturation...

Seminal extracellular vesicles (EVs) contain different subgroups which have diverse effects on sperm function. However, the effect of seminal EVs-especially its subgroups, on the endometrial receptivity was largely unknown. Here, we found that the seminal EVs could be divided into high-density EV (EV-H)、medium density EV (EV-M) and low-density EV (EV-L), after purification using iodixanol. Then we demonstrated that EV-H could promote the expression and secretion of leukemia inhibitor factor (LIF) in human endometrial cells...

Acromegaly and gigantism are disorders caused by hypersecretion of growth hormone (GH), usually from pituitary adenomas. Although somatostatin analogues (SSA), dopamine agonists and GH receptor antagonist are important therapeutic agents, all of these have issues with their effectiveness, safety, and/or convenience of use. To overcome these, we developed a GH-specific potent neutralizing mouse monoclonal antibody (mAb) named 13H02. 13H02 selectively bound to both human and monkey GH with high affinity, and strongly inhibited the biological activity of GH in the Nb2 rat lymphoma cell proliferation assay...

No abstract text is available yet for this article.

BACKGROUND: Obesity is a risk factor for the development of papillary thyroid cancer (PTC). However, the molecular mechanisms by which obesity promotes PTC is unclear. This study aims to identify adipokines that are linked to PTC progression. METHODS: An adipokine antibody array was used to determine the serum levels of 40 adipokines in normal-weight and obese PTC patients. ELISA was used to determine the serum levels of adiponectin. Recombinant human adiponectin was produced by human adipose-derived stem cells (ASCs) and used to treat PTC cells...

The neuroendocrine system that controls the pre-ovulatory surge of gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH), which triggers ovulation in female mammals, is sexually differentiated in rodents. A transient increase in circulating testosterone levels in male rats within a few hours of birth is primarily responsible for the defeminization of anteroventral periventricular nucleus (AVPV) kisspeptin neurons, which are critical regulators of the GnRH/LH surge. The present study aimed to determine if neonatal estradiol-17β (E2) converted from testosterone by aromatase primarily causes the defeminization of AVPV kisspeptin neurons and the surge of GnRH/LH in male rodents...

Macromastia is an excessive, rapid or slow growth of breast tissue in one or both breasts. While macromastia represents a benign lesion, it may cause breast, shoulder, back and neck pain, poor posture, infections, and loss of nipple sensation. The pathogenesis of macromastia or hypertrophy of mammary tissue remains poorly understood. The purpose of this study is to investigate the immunohistochemical expression of several hormone receptors that may potentially influence the growth of breast tissue in women with macromastia...

A series of well-described anabolic and catabolic neuropeptides are known to provide short-term, homeostatic control of energy balance. The mechanisms that govern long-term, rheostatic control of regulated changes in energy balance are less well characterized. Using the robust and repeatable, seasonal changes in body mass observed in Siberian hamsters, this report examined the role of prolactin to provide long-term rheostatic control of body mass and photoinduced changes in organ mass (i.e., kidney, brown adipose tissue, uterine and spleen)...

No abstract text is available yet for this article.

Organophosphate esters (OPEs) are used primarily as flame retardants and plasticizers. Previously, we reported that adrenal cells are important targets of individual OPEs. However, real life exposures are to complex mixtures of these chemicals. To address this, we exposed H295R human adrenal cells to varying dilutions (1/1000 K to 1/3 K) of a Canadian household dust based OPE mixture for 48 h and evaluated effects on phenotypic, lipidomic, and functional parameters. Using a high-content screening approach, we assessed phenotypic markers at mixture concentrations at which there was greater than 70% cell survival; the most striking effect of the OPE mixture was a 2...