Reproduction in males is governed by hormonal communication linking the brain and the; testis. The brainintegrates cues from the environment and hormonal signals from the testis to govern the secretion ofgonadotropin-releasing hormone (GnRH) from neurons in the forebrain and hypothalamus. GnRH directsthe synthesis and release of the gonadotropins, LH and FSH, which exert control over testicular function.Testosterone from the testis then acts on the brain to provide the primary signal to regulate sexualdifferentiation, gonadotropin secretion, gender identity, and libido. Androgens, including testosterone andrelated compounds, are being used for male contraception, as well as for the treatment of delayed puberty,hypogonadism, osteoporosis, sexual dysfunction, cachexia and related disorders, and their development anduse will continue to grow as will the demand for more information about their actions on the brain. Theprimary objective of this research is to discover the molecular and cellular basis of testosterone's action inthe forebrain of the male macaque, a primate whose reproductive physiology closely resembles that of man.
The specific aims of this project are focused on learning more about the role of 4 particularneuropeptides- cocaine- and amphetamine-regulated transcript (CART), agouti-related protein (AgRP),melanin-concentrating hormone (MCH), and galanin-like peptide (GALP) in the control of gonadotropinsecretion and as molecular targets for the action of testosterone and other related androgens on the brain.Using systems, cellular, and molecular biological techniques, we will examine the effects of theseneuropeptides on LH secretion, test the hypothesis that the genes coding for the peptides .are targets forandrogen regulation, identify the mechanisms involved in signal transduction, and begin to map the synapticcircuitry linking these particular molecules to GnRH neurons. Understanding the cellular and molecularactions of androgens in the brain of a primate, whose reproductive physiology is similar to humans, is thefirst step toward the goal of putting androgenic compounds into use that have maximum therapeutic benefitswith minimal deleterious side effects. Over time, the knowledge provided by these studies will be an aide tothe development of improved strategies for addressing the problems of overpopulation, increasing optionsfor family planning, and treating disorders of reproduction in men.
Showing the most recent 10 out of 110 publications
