Prenatal Androgen Treatment Does Not Alter the Firing Activity of Hypothalamic Arcuate Kisspeptin Neurons in Female Mice
Abstract
Neuroendocrine control of reproduction is disrupted in many individuals with polycystic ovary syndrome (PCOS), who present with increased luteinizing hormone (LH), and presumably gonadotropin-releasing hormone (GnRH), release frequency, and high androgen levels. Prenatal androgenization (PNA) recapitulates these phenotypes in primates and rodents. Female offspring of mice injected with dihydrotestosterone (DHT) on gestational days 16–18 exhibit disrupted estrous cyclicity, increased LH and testosterone, and increased GnRH neuron firing rate as adults. PNA also alters the developmental trajectory of GnRH neuron firing rates, markedly blunting the prepubertal peak in firing that occurs in three-week (3wk)-old controls. GnRH neurons do not express detectable androgen receptors and are thus probably not the direct target of DHT. Rather, PNA likely alters GnRH neuronal activity by modulating upstream neurons, such as hypothalamic arcuate neurons co-expressing kisspeptin, neurokinin B (gene Tac2), and dynorphin, also known as KNDy neurons. We hypothesized PNA treatment changes firing rates of KNDy neurons in a similar age-dependent manner as GnRH neurons. We conducted targeted extracellular recordings (0.5–2 h) of Tac2-identified KNDy neurons from control and PNA mice at 3wks of age and in adulthood. About half of neurons were quiescent (in vivonetworks as critical drivers of altered GnRH firing rates in PNA mice.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 01, 2021
- Source ID
- 10.1523/eneuro.0306-21.2021
Entities
People
- Amanda G. Gibson
- Jennifer Jaime
- Laura L. Burger
- Suzanne M Moenter
Organizations
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
- United States Department of Defense