Chemogenetic Suppression of GnRH Neurons during Pubertal Development Can Alter Adult GnRH Neuron Firing Rate and Reproductive Parameters in Female Mice

  title={Chemogenetic Suppression of GnRH Neurons during Pubertal Development Can Alter Adult GnRH Neuron Firing Rate and Reproductive Parameters in Female Mice},
  author={Eden A. Dulka and R. A. Defazio and S. Moenter},
Abstract Gonadotropin-releasing hormone (GnRH) neurons control anterior pituitary, and thereby gonadal, function. GnRH neurons are active before outward indicators of puberty appear. Prenatal androgen (PNA) exposure mimics reproductive dysfunction of the common fertility disorder polycystic ovary syndrome (PCOS) and reduces prepubertal GnRH neuron activity. Early neuron activity can play a critical role in establishing circuitry and adult function. We tested the hypothesis that changing… Expand


Ovarian androgens maintain high GnRH neuron firing rate in adult prenatally androgenized female mice.
The results suggest prenatal androgen exposure programs marked changes in GnRH neuron regulation by homeostatic steroid feedback, which renders activity in adulthood dependent upon ongoing exposure to elevated ovarian androgens. Expand
Prepubertal Development of Gonadotropin-Releasing Hormone Neuron Activity Is Altered by Sex, Age, and Prenatal Androgen Exposure
Preubertal activity may play a role in establishing sexually differentiated neuronal networks upstream of GnRH neurons; androgen-induced changes during this time may contribute to the adult prenatally androgenized PNA, and possibly PCOS, phenotype. Expand
Prepubertal Development of GABAergic Transmission to Gonadotropin-Releasing Hormone (GnRH) Neurons and Postsynaptic Response Are Altered by Prenatal Androgenization
Evidence is provided that PNA alters prepubertal development of the GABAergic network afferent to GnRH neurons, including both the presynaptic organization and postsynaptic response, which may contribute to reproductive dysfunction in adults. Expand
Prenatal androgens alter GABAergic drive to gonadotropin-releasing hormone neurons: implications for a common fertility disorder.
The ability of prenatal steroid exposure to initiate changes that alter functional inputs to GnRH neurons in adults has important implications for understanding the regulation of normal reproduction as well as the hypothalamic abnormalities of fertility disorders. Expand
Prenatal androgenization of female mice programs an increase in firing activity of gonadotropin-releasing hormone (GnRH) neurons that is reversed by metformin treatment in adulthood.
It is indicated that PNA causes enhanced firing activity of GnRH neurons and elevated LH that are reversible by meetformin, raising the possibility that central AMPK activation by metformin may play a role in its restoration of reproductive cycles in polycystic ovary syndrome. Expand
Activation of arcuate nucleus GABA neurons promotes luteinizing hormone secretion and reproductive dysfunction: Implications for polycystic ovary syndrome
Unexpectedly blunted HPG axis responses in PNA mice may reflect a history of high frequency GnRH/LH secretion and reduced LH stores, but also raise questions about impaired function within the ARN GABA population and the involvement of other circuits. Expand
Enhancement of a robust arcuate GABAergic input to gonadotropin-releasing hormone neurons in a model of polycystic ovarian syndrome
Evidence for disordered progesterone (P4)-sensitive GABAergic input to GnRH neurons, originating specifically within the arcuate nucleus of the hypothalamus (ARN), is described, defining a previously unidentified neuronal pathway, potentially critical for the steroid hormone feedback control of fertility. Expand
Long‐Term Recordings of Arcuate Nucleus Kisspeptin Neurons Reveal Patterned Activity That Is Modulated by Gonadal Steroids in Male Mice
The observation that KNDy neurons fire in an episodic manner that is regulated by steroid feedback is consistent with a role for these neurons in GnRH pulse generation and regulation. Expand
Neuroendocrine Consequences of Prenatal Androgen Exposure in the Female Rat: Absence of Luteinizing Hormone Surges, Suppression of Progesterone Receptor Gene Expression, and Acceleration of the Gonadotropin-Releasing Hormone Pulse Generator1
The hypothesis that prenatal androgen receptor activation can contribute to the permanent defeminization of the GnRH neurosecretory system, rendering it incapable of initiating GnRH surges, while accelerating basal GnRH pulse generator activity in adulthood is supported. Expand
Olfactory Inputs to Hypothalamic Neurons Controlling Reproduction and Fertility
Chemosensory modulation of LHRH neuronal activity and mating behavior are dramatically impaired in absence of olfactory function, while they appear unaffected in mouse mutants lacking vomeronasal signaling. Expand