Presented By: Department of Psychology
Biopsychology Colloquium
Carol Elias, Associate Professor of Molecular & Integrative Physiology and Obstetrics & Gynecology
Neural Basis for the Metabolic Control of Reproduction
It is well-established that a minimum amount of stored energy is required for normal pubertal development and for reproductive health in adult life. On the other hand, excess energy also negatively impacts the reproductive physiology. Elevated adiposity in women aggravates polycystic ovary syndrome, ovulatory dysfunction and decreases the reproductive capacity. In obese men, fertility is diminished due to altered activity of the hypothalamo-pituitary-gonadal (HPG) axis and defective steroidogenesis. The increasing rates of childhood obesity have been correlated with early puberty and its deleterious consequences. Earlier menarche in girls is associated with increased risk of adult obesity, type 2 Diabetes and breast cancer. Thus, changing levels of key metabolic cues is an essential signal to the onset of puberty and the adequate function of the reproductive system in adult life. The adipocyte hormone leptin signals the amount of energy stored to the HPG axis. Humans and mice with leptin signaling deficiency are obese and infertile, remaining in a pre-pubertal state. However, the neural basis for the primary reproductive actions of leptin remains unclear. Our laboratory has identified the hypothalamic ventral premammillary nucleus (PMV) as an essential relay of leptin action in reproductive physiology. Our working hypothesis is that the PMV has three distinct neuronal components, i.e., one excitatory, one inhibitory, and one synchronizer. The balance among them would determine the responses of the HPG axis to metabolic challenges. In this seminar, we will discuss the findings supporting our hypothesis. We have used viro- and chemo-genetic in mouse models to determine the roles of glutamate neurotransmission (excitatory component) and dopamine transporter-expressing neurons (inhibitory component) in reproductive control. We will also discuss preliminary and ongoing studies indicating the nitric oxide works as a synchronizer component in the activity of the PMV neuronal network.
It is well-established that a minimum amount of stored energy is required for normal pubertal development and for reproductive health in adult life. On the other hand, excess energy also negatively impacts the reproductive physiology. Elevated adiposity in women aggravates polycystic ovary syndrome, ovulatory dysfunction and decreases the reproductive capacity. In obese men, fertility is diminished due to altered activity of the hypothalamo-pituitary-gonadal (HPG) axis and defective steroidogenesis. The increasing rates of childhood obesity have been correlated with early puberty and its deleterious consequences. Earlier menarche in girls is associated with increased risk of adult obesity, type 2 Diabetes and breast cancer. Thus, changing levels of key metabolic cues is an essential signal to the onset of puberty and the adequate function of the reproductive system in adult life. The adipocyte hormone leptin signals the amount of energy stored to the HPG axis. Humans and mice with leptin signaling deficiency are obese and infertile, remaining in a pre-pubertal state. However, the neural basis for the primary reproductive actions of leptin remains unclear. Our laboratory has identified the hypothalamic ventral premammillary nucleus (PMV) as an essential relay of leptin action in reproductive physiology. Our working hypothesis is that the PMV has three distinct neuronal components, i.e., one excitatory, one inhibitory, and one synchronizer. The balance among them would determine the responses of the HPG axis to metabolic challenges. In this seminar, we will discuss the findings supporting our hypothesis. We have used viro- and chemo-genetic in mouse models to determine the roles of glutamate neurotransmission (excitatory component) and dopamine transporter-expressing neurons (inhibitory component) in reproductive control. We will also discuss preliminary and ongoing studies indicating the nitric oxide works as a synchronizer component in the activity of the PMV neuronal network.
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