scholarly journals Firing patterns of gonadotropin-releasing hormone neurons are sculpted by their biologic state

2020 ◽  
Vol 7 (8) ◽  
pp. 201040
Author(s):  
Jonathon Penix ◽  
R. Anthony DeFazio ◽  
Eden A. Dulka ◽  
Santiago Schnell ◽  
Suzanne M. Moenter
Keyword(s):  
Action Potential ◽  
Polycystic Ovary ◽  
Brain Slices ◽  
Gonadotropin Releasing Hormone ◽  
Neuron Activity ◽  
Interval Order ◽  
Short Term ◽  
Firing Patterns ◽  
Releasing Hormone ◽  
Gnrh Neurons

Gonadotropin-releasing hormone (GnRH) neurons form the final pathway for the central neuronal control of fertility. GnRH is released in pulses that vary in frequency in females, helping drive hormonal changes of the reproductive cycle. In the common fertility disorder polycystic ovary syndrome (PCOS), persistent high-frequency hormone release is associated with disrupted cycles. We investigated long- and short-term action potential patterns of GnRH neurons in brain slices before and after puberty in female control and prenatally androgenized (PNA) mice, which mimic aspects of PCOS. A Monte Carlo (MC) approach was used to randomize action potential interval order. Dataset distributions were analysed to assess (i) if organization persists in GnRH neuron activity in vitro , and (ii) to determine if any organization changes with development and/or PNA treatment. GnRH neurons in adult control, but not PNA, mice produce long-term patterns different from MC distributions. Short-term patterns differ from MC distributions before puberty but become absorbed into the distributions with maturation, and the distributions narrow. These maturational changes are blunted by PNA treatment. Firing patterns of GnRH neurons in brain slices thus maintain organization dictated at least in part by the biologic status of the source and are disrupted in models of disease.

scholarly journals Lack of sex differences in gonadotropin-releasing hormone (GnRH) neuron potassium currents and excitability

2021 ◽  
Author(s):  
R Anthony DeFazio ◽  
Suzanne M Moenter
Keyword(s):  
Action Potential ◽  
Negative Feedback ◽  
Positive Feedback ◽  
Brain Slices ◽  
Potassium Currents ◽  
Gonadotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Voltage Gated ◽  
Gnrh Neurons ◽  
Gnrh Release

Gonadotropin-releasing hormone (GnRH) drives pituitary secretion of luteinizing hormone (LH) and follicle-stimulating hormone, which in turn regulate gonadal functions including steroidogenesis. The pattern of GnRH release and thus fertility depend on gonadal steroid feedback. Under homeostatic (negative) feedback conditions, removal of the gonads from either females or males increases the amplitude and frequency of GnRH release and alters the long-term firing pattern of these neurons in brain slices. The neurobiological mechanisms intrinsic to GnRH neurons that are altered by homeostatic feedback are not well studied and have not been compared between sexes. During estradiol positive feedback, which is unique to females, there are correlated changes in voltage-gated potassium currents and neuronal excitability. We thus hypothesized these same mechanisms would be engaged in homeostatic negative feedback. Voltage-gated potassium channels play a direct role in setting excitability and action potential properties. Whole-cell patch-clamp recordings of GFP-identified GnRH neurons in brain slices from sham-operated and castrated adult female and male mice were made to assess fast (IA) and slow (IK) inactivating potassium currents as well as action potential properties. Surprisingly, no changes were observed in most potassium current properties, input resistance or capacitance and this was reflected in a lack of differences in excitability and specific action potential properties. These results support the concept that, in contrast to positive feedback, steroid negative feedback regulation of GnRH neurons in both sexes is likely conveyed to GnRH neurons via mechanisms that do not induce major changes in the biophysical properties of these cells.

Short-term effects of gonadotropin-releasing hormone analogue treatment on leptin, ghrelin and peptide YY in girls with central precocious puberty

2021 ◽  
Vol 34 (4) ◽  
pp. 479-484
Author(s):  
Piyathida Wijarn ◽  
Preamrudee Poomthavorn ◽  
Patcharin Khlairit ◽  
Sarunyu Pongratanakul ◽  
Laor Chailurkit ◽  
...  
Keyword(s):  
Precocious Puberty ◽  
Peptide Yy ◽  
Central Precocious Puberty ◽  
Gonadotropin Releasing Hormone ◽  
Hormone Analogue ◽  
Short Term ◽  
Serum Leptin ◽  
Releasing Hormone ◽  
Gonadotropin Releasing Hormone Analogue ◽  
Before And After

Abstract Objectives To determine appetite-regulating hormone levels in girls with central precocious puberty (CPP) before and after 20 weeks of gonadotropin-releasing hormone analogue (GnRH-A) treatment. Methods Eighteen newly diagnosed CPP girls were enrolled. Body composition measured by bioelectrical impedance analysis and GnRH-A test were performed with fasting serum leptin, ghrelin and peptide YY (PYY) measurements at baseline (before) and after 20 weeks of GnRH-A treatment. Results Following GnRH-A treatment, all patients had prepubertal gonadotropin and estradiol levels. Mean (SD) fat mass index (FMI) was significantly increased from 4.5 (1.7) to 5.0 (1.8) kg/m2 after treatment. Also, median (IQR) serum leptin level was significantly increased from 6.9 (4.2–8.6) to 7.4 (5.3–13.1) ng/mL. FMI had a positive correlation with serum leptin level (r=0.64, p=0.004). In contrast, no significant changes of serum ghrelin and PYY levels were observed. Conclusions Decreased estrogen following short-term GnRH-A treatment in CPP girls may cause an increase in appetite and consequently an elevation of FMI. Increased serum leptin may be a result of having increased FMI secondary to an increase in appetite.

Gonadotropin releasing hormone agonists vs. antagonists in women with polycystic ovary disease undergoing ICSI

2007 ◽  
Vol 88 ◽  
pp. S122
Author(s):  
K. Sofuoglu ◽  
B. Kars ◽  
E. Caliskan ◽  
D. Oztekin ◽  
N. Tug ◽  
...  
Keyword(s):  
Polycystic Ovary ◽  
Gonadotropin Releasing Hormone ◽  
Releasing Hormone

scholarly journals Effect of Inflammation on Female Gonadotropin-Releasing Hormone (GnRH) Neurons: Mechanisms and Consequences

2020 ◽  
Vol 21 (2) ◽  
pp. 529 ◽  
Author(s):  
Klaudia Barabás ◽  
Edina Szabó-Meleg ◽  
István M. Ábrahám
Keyword(s):  
Suppressive Effect ◽  
Gonadotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Inflammatory Signals ◽  
Cholinergic Pathway ◽  
Gnrh Neurons ◽  
Functional Consequences ◽  
Anti Inflammatory ◽  
The Impact

Inflammation has a well-known suppressive effect on fertility. The function of gonadotropin-releasing hormone (GnRH) neurons, the central regulator of fertility is substantially altered during inflammation in females. In our review we discuss the latest results on how the function of GnRH neurons is modified by inflammation in females. We first address the various effects of inflammation on GnRH neurons and their functional consequences. Second, we survey the possible mechanisms underlying the inflammation-induced actions on GnRH neurons. The role of several factors will be discerned in transmitting inflammatory signals to the GnRH neurons: cytokines, kisspeptin, RFamide-related peptides, estradiol and the anti-inflammatory cholinergic pathway. Since aging and obesity are both characterized by reproductive decline our review also focuses on the mechanisms and pathophysiological consequences of the impact of inflammation on GnRH neurons in aging and obesity.

scholarly journals The Role of the Brain in the Pathogenesis and Physiology of Polycystic Ovary Syndrome (PCOS)

2019 ◽  
Vol 7 (8) ◽  
pp. 84 ◽  
Author(s):  
Coutinho ◽  
Kauffman
Keyword(s):  
Animal Models ◽  
Polycystic Ovary Syndrome ◽  
Neural Circuit ◽  
Polycystic Ovary ◽  
Pulse Frequency ◽  
Reproductive Age ◽  
Neuron Activity ◽  
Ovary Syndrome ◽  
Gnrh Neurons ◽  
Reproductive Endocrine

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder, affecting at least 10% of women of reproductive age. PCOS is typically characterized by the presence of at least two of the three cardinal features of hyperandrogenemia (high circulating androgen levels), oligo- or anovulation, and cystic ovaries. Hyperandrogenemia increases the severity of the condition and is driven by increased luteinizing hormone (LH) pulse secretion from the pituitary. Indeed, PCOS women display both elevated mean LH levels, as well as an elevated frequency of LH pulsatile secretion. The abnormally high LH pulse frequency, reflective of a hyperactive gonadotropin-releasing hormone (GnRH) neural circuit, suggests a neuroendocrine basis to either the etiology or phenotype of PCOS. Several studies in preclinical animal models of PCOS have demonstrated alterations in GnRH neurons and their upstream afferent neuronal circuits. Some rodent PCOS models have demonstrated an increase in GnRH neuron activity that correlates with an increase in stimulatory GABAergic innervation and postsynaptic currents onto GnRH neurons. Additional studies have identified robust increases in hypothalamic levels of kisspeptin, another potent stimulator of GnRH neurons. This review outlines the different brain and neuroendocrine changes in the reproductive axis observed in PCOS animal models, discusses how they might contribute to either the etiology or adult phenotype of PCOS, and considers parallel findings in PCOS women.

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