A5035033862- Hypothalamic control of reproductive hormones
- Plant Reproductive Biology
- Regulation of Appetite and Obesity
- Neurobiology and Insect Physiology Research
- Neuroendocrine regulation and behavior
- Estrogen and related hormone effects
- Neuropeptides and Animal Physiology
- Biochemical Analysis and Sensing Techniques
- Ovarian function and disorders
- Stress Responses and Cortisol
- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Plant Molecular Biology Research
- Growth Hormone and Insulin-like Growth Factors
- Adipose Tissue and Metabolism
- Menopause: Health Impacts and Treatments
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Biochemical and Structural Characterization
- Mesenchymal stem cell research
- Axon Guidance and Neuronal Signaling
- Exercise and Physiological Responses
- Epigenetics and DNA Methylation
- Adipokines, Inflammation, and Metabolic Diseases
- Sexual Differentiation and Disorders
Oregon Health & Science University
2014-2025
Oregon National Primate Research Center
2002-2015
University of Portland
2006
University of California, San Francisco
2003
Vollum Institute
1996
Classically, 17β-estradiol (E 2 ) is thought to control homeostatic functions such as reproduction, stress responses, feeding, sleep cycles, temperature regulation, and motivated behaviors through transcriptional events. Although it increasingly evident that E can also rapidly activate kinase pathways have multiple downstream actions in CNS neurons, the receptor(s) signal transduction involved not been identified. We discovered alter μ-opioid GABA neurotransmission nontranscriptional events...
Kisspeptin (Kiss1) and neurokinin B (NKB) (encoded by the Kiss1 Tac2 genes, respectively) are indispensable for reproduction. In female of many species, neurons in arcuate nucleus (ARC) coexpress dynorphin A NKB. Such cells have been termed Kiss1/NKB/Dynorphin (KNDy) neurons, which thought to mediate negative feedback regulation GnRH/LH secretion 17β-estradiol. However, we less knowledge about molecular physiology Kiss1/Kiss1-expressing ARC male. Our work focused on adult male mouse, where...
Hypothalamic proopiomelanocortin (POMC) neurons are critical for controlling homeostatic functions in the mammal. We used a transgenic mouse model which POMC were labeled with enhanced green fluorescent protein to perform visualized, whole-cell patch recordings from prepubertal female hypothalamic slices. The POMC-enhanced expressed same endogenous conductances (a transient outward K+ current and hyperpolarization-activated, cation current) that have been described guinea pig neurons. In...
Estrogens are involved in the hypothalamic control of multiple homeostatic functions including reproduction, stress responses, energy metabolism, sleep cycles, temperature regulation, and motivated behaviors. The critical role 17β-estradiol (E 2 ) is evident hypoestrogenic states (e.g., postmenopause) which many these go awry. actions E brain have been attributed to activation estrogen receptors α β through nuclear, cytoplasmic, or membrane actions. However, we identified a putative...
Abstract Hypothalamic kisspeptin neurons are critical for driving reproductive function, but virtually nothing is known about their endogenous electrophysiological properties and the effects of leptin on excitability. Therefore, we used slice preparation from female guinea pigs to study conductances neurons. We targeted arcuate using visualized-patch whole-cell recording identified immuocytochemical staining or single cell RT-PCR. also harvested dispersed analysis expression channel...
Neurons that produce kisspeptin play a critical role in reproduction. However, understanding the molecular physiology of neurons has been limited by lack an vivo marker for those cells. Here, we report development Kiss1-CreGFP knockin mouse, wherein endogenous Kiss1 promoter directs expression Cre recombinase-enhanced green fluorescent protein (GFP) fusion protein. The pattern GFP brain recapitulates what described earlier male and female with prominent arcuate nucleus (ARC) (in both sexes)...
Tachykinins are comprised of the family related peptides, substance P (SP), neurokinin A (NKA), and B (NKB). NKB has emerged as regulator kisspeptin release in arcuate nucleus (ARC), whereas roles SP NKA reproduction remain unknown. This work explores central regulation GnRH release. First, infusion specific agonists for receptors (neurokinin receptor 1, NK1R), (NK2R) (NK3R) each induced gonadotropin adult male ovariectomized, estradiol-replaced female mice, which was absent Kiss1r−/−...
Kisspeptin (Kiss1) neurons are essential for reproduction, but their role in the control of energy balance and other homeostatic functions remains unclear. Proopiomelanocortin (POMC) agouti-related peptide (AgRP) neurons, located arcuate nucleus (ARC) hypothalamus, integrate numerous excitatory inhibitory inputs to ultimately regulate homeostasis. Given that POMC AgRP contacted by Kiss1 ARC (Kiss1(ARC)) they express androgen receptors, Kiss1(ARC) may mediate orexigenic action testosterone...
Abstract Puberty is regulated by epigenetic mechanisms and highly sensitive to metabolic nutritional cues. However, the pathways mediating effects of nutrition obesity on pubertal timing are unknown. Here, we identify Sirtuin 1 (SIRT1), a fuel-sensing deacetylase, as molecule that restrains female puberty via repression puberty-activating gene, Kiss1 . SIRT1 expressed in hypothalamic neurons suppresses expression. interacts with Polycomb silencing complex decrease promoter activity. As...
The neuropeptides tachykinin2 (Tac2) and kisspeptin (Kiss1) in hypothalamic arcuate nucleus Kiss1 (Kiss1ARH) neurons are essential for pulsatile release of GnRH reproduction. Since 17β-estradiol (E2) decreases Tac2 mRNA expression Kiss1ARH neurons, the role during E2-driven anorexigenic states their coordination POMC NPY/AgRP feeding circuits have been largely ignored. Presently, we show that E2 augmented excitability by amplifying Cacna1g, Hcn1 Hcn2 T-type calcium h-currents. increased...
The identification of loss-of-function mutations in MKRN3 patients with central precocious puberty association the decrease expression medial basal hypothalamus mice before initiation reproductive maturation suggests that is acting as a brake on gonadotropin-releasing hormone (GnRH) secretion during childhood. In current study, we investigated mechanism by which prevents premature manifestation pubertal process. We showed that, mice, high rats and nonhuman primates early life, decreases...
Gonadotropin-releasing hormone (GnRH) is released in a pulsatile manner that dependent on circulating 17β-estradiol (E2) and glucose concentrations. However, the intrinsic conductances responsible for episodic firing pattern underlying release effects of E2 these are primarily unknown. Whole-cell recordings from mouse enhanced green fluorescent protein-GnRH neurons revealed K ATP channel opener diazoxide induced an outward current was antagonized by sulfonylurea receptor 1 (SUR1) blocker...
γ-Aminobutyric acid (GABA) is one of the most important neurotransmitters that regulate excitability GnRH neurons. Numerous studies have shown GABA activates Cl− currents in neurons, and these effects are antagonized by GABAA receptor antagonists. The GABAB a heterodimer composed R1 R2, although both subunits been localized nothing known about cellular signaling this Gαi,o-coupled Using whole-cell recordings from mouse enhanced green fluorescent protein-GnRH we found agonist baclofen...
T-type calcium channels are responsible for generating low-threshold spikes that facilitate burst firing and neurotransmitter release in neurons. Gonadotropin-releasing hormone (GnRH) neurons exhibit firing, but the underlying conductances not known. Previously, we found 17β-estradiol (E2) increases channel expression excitability of hypothalamic arcuate nucleus Therefore, used ovariectomized oil- or E2-treated EGFP (enhanced green fluorescent protein)–GnRH mice to explore E2 regulation GnRH...
The hypothalamus is a key region of the central nervous system involved in control homeostasis, including energy and core body temperature (Tc). 17β-Estradiol (E2) regulates Tc, part, via actions basal preoptic area. E2 primarily controls hypothalamic functions nuclear steroid receptors, estrogen receptor α/β. However, we have previously described an E2-responsive, Gq-coupled membrane that reduces postsynaptic inhibitory γ-aminobutyric acid-ergic tone attenuates postovariectomy weight gain...
Besides its quintessential role in reproduction, 17β-estradiol (E 2 ) is a potent anorexigenic hormone. E and the selective G q -coupled membrane estrogen receptor (Gq-mER) ligand STX rapidly increase excitability proopiomelanocortin (POMC) neurons by desensitizing coupling of GABA B receptors to protein-coupled inwardly rectifying K + channels (GIRKs), which upon activation elicit hyperpolarizing outward current. However, it unknown whether can modulate signaling neuropeptide Y...
Kisspeptin (Kiss1) neurons in the rostral periventricular area of third ventricle (RP3V) provide excitatory drive to gonadotropin-releasing hormone (GnRH) control fertility. Using whole cell patch clamp recording and single-cell (sc)RT-PCR techniques targeting Kiss1-CreGFP or tyrosine hydroxylase (TH)-EGFP neurons, we characterized biophysical properties these identified critical intrinsic required for burst firing 17β-estradiol (E2)-treated, ovariectomized female mice. One-fourth RP3V Kiss1...
Estrogen affects the electrophysiological properties of a number hypothalamic neurons by modulating K(+) channels via rapid membrane actions and/or changes in gene expression. The interaction between these pathways (membrane vs. transcription) ultimately determines effects estrogen on functions. Using suppression subtractive hybridization, we produced cDNA library estrogen-regulated, brain-specific guinea pig genes, which included subunits from three prominent K+ (KCNQ5, Kir2.4, Kv4.1, and...
During the reproductive cycle, fluctuations in circulating estrogens affect multiple homeostatic systems controlled by hypothalamic neurons. Two of these neuronal populations are arcuate proopiomelanocortin and neuropeptide Y neurons, which control energy homeostasis feeding. Estradiol modulates neurons either through classical estrogen receptors (ERs) to gene transcription or a G protein-coupled receptor (mER) activating signaling pathways. To differentiate between two divergent ER-mediated...
In vitro slice studies have revealed that there are significant differences in the spontaneous firing activity between anteroventral periventricular/periventricular preoptic nucleus (AVPV/PeN) and arcuate (ARC) kisspeptin (Kiss1) neurons females. Although both populations express similar endogenous conductances, we discovered AVPV/PeN Kiss1 a subthreshold, persistent sodium current (INaP) dramatically alters their activity. Based on whole-cell recording of Kiss1-Cre-green fluorescent protein...
Insulin resistance is at the core of metabolic syndrome, and men exhibit a higher incidence syndrome than women in early adult life, but this sex advantage diminishes sharply when reach postmenopausal state. Because 17β-estradiol (E2) augments excitability anorexigenic proopiomelanocortin (POMC) neurons, we investigated neuroprotective effects E2 against insulin POMC neurons from diet-induced obese (DIO) female male mice. The efficacy to activate canonical transient receptor potential 5...