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Bisphenol S (BPS) affects terminal folliculogenesis by impairing steroidogenesis in granulosa cells from different species. Nevertheless, limited data are available on its effects during basal folliculogenesis. In this study, we evaluate in vitro the effects of a long-term BPS exposure on a model of basal follicular development in a mono-ovulatory species. We cultured ovine preantral follicles (180–240 μm, n = 168) with BPS (0.1 μM (possible human exposure dose) or 10 μM (high dose)) and monitored antrum appearance and follicular survival and growth for 15 days. We measured hormonal secretions (oestradiol (at day 13 [D13]), progesterone and anti-Müllerian hormone [D15]) and expression of key follicular development and redox status genes (D15) in medium and whole follicles, respectively. BPS (0.1 µM) decreased oestradiol secretion compared with the control (−48.8%, p < 0.001), without significantly impairing antrum appearance, follicular survival and growth, anti-Müllerian hormone and progesterone secretion and target gene expression. Thus, BPS could also impair oestradiol secretion during basal folliculogenesis as it is the case during terminal folliculogenesis. It questions the use of BPS as a safe BPA substitute in the human environment. More studies are required to elucidate mechanisms of action of BPS and its effects throughout basal follicular development.

Endometriosis (ENDO) and poor ovarian response (POR) represent challenging conditions in assisted reproduction. Both, associated with altered follicular fluid (FF) composition, specifically impact on granulosa cell (GC) function in an incompletely understood way. GCs from male factor (MF, n = 30), ENDO (n = 38), and POR (n = 27) patients were cultured in media supplemented with FF from each group (FF-MF, FF-ENDO, FF-POR). Proliferation, morphology, and secretory activity (cortisol, estradiol, progesterone, IL-6) were assessed. GC proliferation depended primarily on FF origin, being highest with FF-ENDO, intermediate with FF-POR, and lowest with FF-MF. Morphological analysis revealed enrichment of muscle-like and fibroblast-like morphologies under FF-ENDO and FF-POR, suggestive of dysregulated luteinization and extracellular matrix remodeling. Secretory activity reflected a complex interplay between GC origin and FF type: IL-6 was strongly induced by FF-MF and FF-POR but consistently suppressed by FF-ENDO; cortisol and estradiol were generally consumed, while progesterone synthesis was largely confined to MF-GCs, with only variable induction in ENDO-GCs exposed to FF-POR. These findings indicate that pathological FF milieus reprogram GC behavior in distinct ways, with potential consequences for luteal function and oocyte competence. Identifying the molecular mediators of these alterations may guide tailored strategies to improve ART outcomes in ENDO and POR patients.

The brain (hypothalamus) directs hormone secretion by the pituitary gland via burst-like (pulsatile) release of specific peptides at inferentially random times. These pulsatile signals supervise growth, reproduction, lactation, stress adaptations, water balance and immune responses. However, hypothalamic molecules are diluted >> 3000-fold in systemic blood, leaving pituitary-hormone pulses as measurable surrogates. The latter (roughly) mirror hypothalamic peptide bursts on a 1:1 basis, albeit being observed in a noisy environment. As a window to the brain, one must accurately recover the pulse (onset) times, and thereby estimate hormone secretion and kinetic parameters (θ∈Θ¯\\theta \\in \\overline {\\Theta }) without distortion. Based upon limited observed data, one would like to obtain probability statements about underlying pulsatility, secretion and kinetics. Moreover, to be applicable in today’s clinical setting, it is important that any such procedure require minimal or no human input. We propose and justify the following method. First, the data (a pituitary hormone concentration time-profile) is “selectively smoothed” by a nonlinear diffusion equation, whose diffusion coefficient is inversely related to the degree of rapid increase. This procedure generates a collection of potential pulse time sets (T)(\\mathbb {T}). Then, via an algorithm which alternates between a Metropolis algorithm on T\\mathbb {T} and a time-homogeneous diffusion process on Θ¯\\overline {\\Theta }, a compact manifold with boundary, simulation from an appropriately formulated (posterior) probability measure is achieved. The method is applied to recover the underlying structure of brain-pituitary regulation in disease and aging.

Background Operative resection is the only curative treatment for pheochromocytomas. Inhibition of the phosphatidylinositol-3 kinase (PI3K)-Akt pathway has been shown to be an effective treatment of neuroendocrine (NE) tumors in vitro. We hypothesized that inhibition of the PI3K-Akt pathway would be a viable strategy to inhibit growth and hormonal secretion in pheochromocytoma cells. Methods Sixteen pheochromocytomas were analyzed for expression of phosphorylated Akt and the NE marker achaete scute complex-like 1 (ASCL1). Pheochromocytoma PC-12 cells were treated with up to 100 μM of the PI3K-specific inhibitor LY294002 for 48 h. Western blot analysis was used to measure phosphorylated Akt, total Akt, ASCL1, chromogranin A (CgA), and markers of apoptosis. Growth was assessed by a methylthiazolyldiphenyl-tetrazolium (MTT) bromide cellular proliferation assay for six days. Results Human pheochromocytomas expressed significant amounts of phosphorylated Akt, and there was a significant correlation between malignant pheochromocytomas and the amount of expressed ASCL1. LY294002 significantly inhibited the PI3K-Akt pathway. Treatment led to a dose-dependent decrease in both ASCL1 and CgA, indicating an alteration in the NE phenotype and hormonal suppression. Treatment decreased cellular proliferation, and cleavage of the apoptotic markers caspase-3 and PARP was observed. Conclusions Human pheochromocytoma tumor samples express high levels of phosphorylated Akt. LY294002 effectively inhibits the PI3K-Akt pathway, suppresses NE tumor markers, and decreases cellular proliferation via apoptosis in vitro. Inhibition of the PI3K pathway may represent a new strategy in the treatment of pheochromocytomas.

A stochastic biomathematical model for the male reproductive hormone system (gonadotropin-releasing hormone, luteinizing hormone, and testosterone) is developed. Hormone secretion occurs as either a continuous release, a pulsatile release, or a combination thereof; in the latter two, hormone molecules are stored and later released. Each form of release is represented within the male system. The model begins at the cellular level of hormone synthesis, aggrandizes to the level of the gland and secretion, and finally to the level of elimination and circulation in the blood. The model consists of a system of stochastic integrodifferential equations which describe the nonlinear time-delayed feedback from concentrations (of the various hormones) on their rates of hormone synthesis. A stochastic formulation is established, showing that the various imposed structures are consistent with one another. Computer experiments are performed and compared to analogous clinical experiments (where components are decoupled via pharmacological intervention) to show the dynamic range of the model and its potential usefulness (e.g., assessing the pathway of the circadian rhythm).

The suprachiasmatic nucleus (SCN) sits at the peak of a hierarchy of clocks found throughout the body. The central clock has to coordinate these molecular clocks and also to regulate directly the temporal patterning of physiology and behavior. Centrally, the SCN secrete neuropeptides directly and SCN neurons project through multisynaptic pathways to arousal and sleep control centers. Through these neural and hormonal pathways, the SCN can direct the temporal patterning of ANS and hormonal secretions that constitute the main ways the nervous system communicates with rest of the body. Furthermore, by regulating the timing of behaviors such as sleep, activity, and feeding, the circadian circuit will indirectly have a major impact on every cell in our body. This chapter allows us to conclude that the SCN is the master circadian clock in mammals and provides a level of confidence for a localization of function which is unusual in nervous system.

During the last decade there has been a proliferation of all types of enduro-sports amongst adults and children both in the recreational or competitive field. These enduro-sports include aerobic dance workouts, canoeing, running, the triathlon, cycling and swimming. There has been a recent upsurge of interest in the research of the physiological effects of running with prolific metabolic, renal, cardiovascular and pulmonary responses to exercise have been well researched.

First-generation somatostatin analogs (SSAs), such as octreotide (OCT), are the first line medical therapy for acromegaly. Pasireotide (PAS), a newly developed SSA, has shown promising results in the treatment of acromegaly. To compare the antisecretory effect of OCT and PAS in primary cultures of growth hormone (GH)-secreting pituitary adenomas (GH-omas). To correlate responses with the adenoma somatostatin receptor (SSTR) profile. The effect of OCT and PAS on GH (and PRL) secretion was tested in 33 GH-oma cultures. SSTR expression was evaluated in adenoma samples. Patients with acromegaly referred to the Erasmus Medical Center (Rotterdam, The Netherlands). OCT and PAS treatment for 72 hours (10 nM). GH (and PRL) concentrations in cell culture media. SSTR expression in adenoma samples. The overall effect of OCT (-36.8%) and PAS (-37.1%) on GH secretion was superimposable. We identified three adenoma groups: PAS+ (PAS more effective than OCT), n = 6; PAS = OCT, n = 22; and OCT+ (OCT more effective than PAS), n = 5. PAS+ adenomas showed lower somatostatin receptor subtype (sst)2 messenger RNA (mRNA) and sst2/sst5 mRNA ratio, compared with the other groups (P < 0.05). PAS inhibited PRL hypersecretion more than OCT (P < 0.01). Overall, OCT and PAS equally reduced GH secretion in vitro. Adenomas with lower sst2 mRNA expression and lower sst2/sst5 mRNA ratio were better responders to PAS compared with OCT. SSTR evaluation in GH-omas may become a tool for tailored SSA treatment in acromegaly.

Abstract Adrenal tumors are commonly discovered incidentally on cross-sectional abdominal imaging performed for reasons other than adrenal mass. Incidence of adrenal tumors increased 10-fold in the past 2 decades, with most diagnosed in older adults. In any patient with a newly discovered adrenal mass, determining whether the adrenal mass is malignant and whether it is hormonally active is equally important to guide the best management. Malignancy is diagnosed in 5% to 8% of patients with adrenal tumors, with a higher risk in young patients, if history of extra-adrenal malignancy, in those with large adrenal tumors with indeterminate imaging characteristics, and in bilateral adrenal tumors. Although overt hormone excess is uncommon in adrenal incidentalomas, mild autonomous cortisol secretion can be diagnosed in up to 30% to 50% of patients. Because autonomous cortisol secretion is associated with increased cardiovascular morbidity and metabolic abnormalities, all patients with adrenal incidentalomas require work up with dexamethasone suppression test. Management of adrenal tumors varies based on etiology, associated comorbidities, and patient’s preference. This article reviews the current evidence on the diagnosis and evaluation of patients with adrenal mass and focuses on management of the most common etiologies of adrenal incidentalomas.

Colostrum plays an essential role in ensuring the survival, growth and health of piglets by providing energy, nutrients, immunoglobulins, growth factors and many other bioactive components and cells. Both colostrum yield and composition are highly variable among sows, yet mechanisms and factors that regulate colostrogenesis are not fully known. Unlike sow milk yield, sow colostrum yield is not highly determined by litter size and suckling intensity but is largely driven by sow-related factors. Colostrum synthesis is under hormonal control, with prolactin and progesterone concentrations prepartum having, respectively, positive and negative influences on colostrum yield. Less is known about the endocrine control of the end of colostrogenesis in swine, which is characterized by the closure of tight junctions in the mammary epithelium and the cessation of transfer of immunoglobulin G (IgG) into lacteal secretions. Recent studies indicate that exogenous hormones may influence colostrogenesis. Inducing parturition by injecting prostaglandin F2α on day 114 of gestation in combination with an oxytocin-like molecule reduced colostrum yield, and injection of prostaglandin F2α alone either reduced colostrum yield or had no effect. Injecting a supraphysiological dose of oxytocin to sows in the early postpartum period delayed the tightening of mammary tight junctions, thereby prolonging the colostral phase and increasing concentrations of IGF-I and IgG and IgA in early milk. The development of strategies to improve colostrum composition in swine through maternal feeding has been largely explored but very few attempts were made to increase colostrum yield. This is most likely because of the difficulty in measuring colostrum yield in swine. The fatty acid content of colostrum greatly depends on the amount of lipids provided in the sow diet during late gestation, whereas the fatty acid profile is largely influenced by the type of lipid being fed to the pregnant sow. Moreover, various ingredients that presumably have immuno-modulating effects (such as fish oil, prebiotics and probiotics) increased concentrations of IgG, IgA and/or IgM in sow colostrum when they were provided during the last weeks of gestation. Finally, there is some evidence that sow nutrition during late gestation may influence colostrum yield but this clearly warrants more research. This review emphasizes that although progress has been made in understanding the control of colostrogenesis in swine, and that strategies exist to manipulate fat and immunoglobulin contents of colostrum, ways to increase colostrum yield are still lacking.