No abstract

Hindbrain-derived stimuli restrain the gonadotropin-releasing hormone (GnRH)-pituitary luteinizing hormone (LH) reproductive neuroendocrine axis during energy insufficiency. Interruption of food intake, planned or unplanned, is emblematic of modern life. This study investigated the premise that the hindbrain energy sensor 5'-adenosine monophosphate-activated protein kinase (AMPK) inhibits reproductive neuroendocrine function in short term, e.g. 18-h food-deprived (FD) estradiol (E)-implanted ovariectomized female rats. Intra-caudal fourth ventricular administration of the AMPK inhibitor Compound C (Cc) reversed FD-induced inhibition of rostral preoptic (rPO) GnRH protein expression and LH release in animals given E to replicate proestrus (high-E dose-, but not metestrus (low-E dose)-stage plasma steroid levels. FD caused Cc-reversible augmentation or diminution of preoptic norepinephrine (NE) activity in high- versus low-E rats, respectively, and AMPK-independent reductions in hypothalamic NE accumulation in the latter. Nitric oxide (NO) and kisspeptin are key stimulatory signals for the preovulatory LH surge. Here, FD inhibited rPO neuronal nitric oxide synthase protein expression in high-, but not low-E-dosed animals. Lateral ventricular delivery of the NO donor 3-morpholinosydnonimine (SIN-1) reversed inhibitory GnRH and LH responses to FD in high-E rats, and normalized rPO Vglut2, anteroventral periventricular KiSS1, and dorsomedial hypothalamic RFRP-3 mRNA and/or protein profiles. Data show that FD curtails reproductive neuroendocrine outflow by hindbrain AMPK-dependent mechanisms in the presence of peak estrous cycle E levels. Results indicate that neural networks linking this sensor to GnRH neurons likely involve NO signaling, which may function upstream of one or more neurotransmitters identified here by SIN-1-reversible inhibitory responses to FD.

No abstract

No abstract

Hindbrain dorsal vagal complex A2 noradrenergic signaling represses the pre-ovulatory luteinizing hormone (LH) surge in response to energy deficiency. Insulin-induced hypoglycemia augments A2 neuron adenosine 5′-monophosphate-activated protein kinase (AMPK) activity and estrogen receptor-beta (ERβ) expression, coincident with LH surge suppression. We hypothesized that ERβ is critical for hypoglycemia-associated patterns of LH secretion and norepinephrine (NE) activity in key reproduction-relevant forebrain structures. The neural mechanisms responsible for tight coupling of systemic energy balance and procreation remain unclear; here, we investigated whether ERβ-dependent hindbrain signals also control glucose counter-regulatory responses to hypoglycemia. Gonadal steroid-primed ovariectomized female rats were pretreated by caudal fourth ventricular administration of the ERβ antagonist 4-[2-phenyl-5,7-bis(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl]phenol (PHTPP) or vehicle at LH surge onset before insulin injection. Western blot analysis of laser-microdissected A2 neurons revealed hypoglycemic augmentation of 5′-monophosphate-activated protein kinase activity and dopamine-β-hydroxylase protein expression; the latter response was attenuated by PHTPP pretreatment. PHTPP regularized LH release, but not preoptic GnRH-I precursor protein expression in insulin-injected rats, and reversed hypoglycemic stimulation of glucagon and corticosterone secretion. Hypoglycemia caused PHTPP-reversible changes in NE and prepro-kisspeptin protein content in the hypothalamic arcuate (ARH), but not anteroventral periventricular nucleus. Results provide novel evidence for ERβ-dependent caudal hindbrain regulation of LH and counter-regulatory hormone secretion during hypoglycemia. That inhibition of LH likely involves mechanisms at the axon terminal that impede GnRH neurotransmission. Data also show that caudal hindbrain ERβ exerts site-specific control of NE activity in forebrain projection sites during hypoglycemia, including the ARH where prepro-kisspeptin may be a target of this signaling.

Total 79 water samples were collected from dug wells located in five different municipal wards of Lalitpur Metropolitan City for assessment of water quality during pre-monsoon season. Physico-chemical parameters (temperature, turbidity, electrical conductivity (EC), pH, total hardness (TH), total alkalinity (TA), chloride, nitrate, ammonia and iron) and microbiological parameters (total coliform and protozoan parasites) were determined using standard protocols.  The range and mean concentrations of the selected parameters in the water samples were found to vary among the selected wards under investigation. The physico-chemical parameters were compared with National Drinking Water Quality Standard (NDWQS) of Nepal and WHO standards. Parameters like pH, chloride, nitrate and iron were found within the permissible limits of NDWQS and WHO guidelines whereas parameter such as ammonia exceeded the maximum permissible limits. Turbidity, EC and TH however showed variable levels within NDWQS and WHO standards. Total coliform count showed only 4 (5.1%) of the total water samples were risk free whereas 43 (54.4%) samples demonstrated maximum microbial contamination and high risk level. Three types of protozoan parasites viz., Cyclospora, Cryptosporidium and Giardia were detected in the water samples. Among the five municipal wards, W. No. 16 has the highest percentage (66.7%) of total coliform contamination in dug wells. Pearson’s correlation analysis was also performed to understand the relationships among the selected water quality parameters. Presence of total coliform and protozoan parasites and exceeding the maximum permissible limits by some physicochemical parameters shows the water quality of dug wells of Lalitpur Metropolitan City is not satisfactory. But, the quality can be improved by effective treatment technologies, planning and policies, strategies and management practices.

Complexes of La(III), Pr(III), Nd(III), Sm(III), Gd(III) and Dy(III) with the Schiff-base, N,N′-di-4-(4’-heptadecyloxybenzoate)salicylidene-1,3-diaminopropane, (abbreviated as H2L) have been synthesized and characterized on the basis of elemental analyses, molar conductance, magnetic, electronic, infrared, 1H and 13C NMR spectral techniques. The nephelauxetic ratio (β), the bonding parameter (b1/2), Sinha’s parameter (%δ) and angular overlap parameter (η) have been calculated from the electronic spectra of Pr(III), Nd(III), Sm(III) and Dy(III) complexes. Infrared and NMR spectral data imply a bi-dentate bonding of the Schiff-base in its zwitterionic form (as LH2) to the Ln(III) ions through two phenolate oxygens, rendering the overall geometry around Ln(III) to distorted square antiprism. Polarized optical microscopy (POM) and differential scanning calorimetry (DSC) shows the liquid crystalline property of the ligand with a nematic (N) mesophase. Among the metal complexes, only that of the Gd(III) exhibits smectic B (SmB) and nematic (N) phases.

Steroid positive-feedback activation of the gonadotropin-releasing hormone (GnRH)-pituitary luteinizing hormone (LH) neuroendocrine axis propagates the pre-ovulatory LH surge, a crucial component of female reproduction. Our work shows that this key event is restrained by inhibitory metabolic input from hindbrain A2 noradrenergic neurons. GnRH neurons express the ultra-sensitive energy sensor adenosine 5’-monophosphate-activated protein kinase (AMPK); here, we investigated the hypothesis that GnRH nerve cell AMPK and peptide neurotransmitter responses to insulin-induced hypoglycemia are controlled by hindbrain lack of the oxidizable glycolytic endproduct L-lactate. Data show that hypoglycemic inhibition of LH release in steroid-primed ovariectomized female rats was reversed by coincident caudal hindbrain lactate infusion. Western blot analyses of laser-microdissected A2 neurons demonstrate hypoglycemic augmentation [Fos, estrogen receptor-beta (ER- ), phosphoAMPK (pAMPK)] and inhibition [dopamine-beta-hydroxylase, GLUT3, MCT2] of protein expression in these cells, responses that were normalized by insulin plus lactate treatment. Hypoglycemia diminished rostral preoptic GnRH nerve cell GnRH-I protein and pAMPK content; the former, but not the latter response was reversed by lactate. Results implicate caudal hindbrain lactoprivic signaling in hypoglycemia-induced suppression of the LH surge, demonstrating that lactate repletion of that site reverses decrements in A2 catecholamine biosynthetic enzyme and GnRH neuropeptide precursor protein expression. Lack of effect of lactate on hypoglycemic patterns of GnRH AMPK activity suggests that this sensor is uninvolved in metabolic-inhibition of positive-feedback - stimulated hypophysiotropic signaling to pituitary gonadotropes.