tion governed by endocrine organs of the pelvis, testes, and ovaries, specialized neurons in the brain and hormones secreted by the “master endocrine organ,” the pituitary, located just beneath the brain, play critical roles in governing reproductive function (see Figure 5-1). Not only do the brain and pituitary coordinate and provide the “central drive” to the reproductive axis throughout life, the brain is also the primary site where environmental factors that modulate reproductive function act.

The region of the brain involved in the regulation of reproductive function as well as many of the body’s other basic homeostatic functions (i.e., control of food intake, growth, response to stress, water balance, metabolic rate) is the hypothalamus. The hypothalamus sits at the base of the brain and is connected by a specialized portal blood system to the pituitary, just below. A population of specialized neurons in the hypothalamus produce the neurotransmitter, gonadotropin-releasing hormone (or GnRH, named for its ability to release the hormones in the pituitary that provide trophic support to the ovaries and testes—the gonadotropins— luteinizing hormone, LH and follicle-stimulating hormone, FSH). GnRH travels via the portal capillaries to the anterior pituitary, where it stimulates the synthesis and release of the pituitary hormones, LH and FSH.

Many neurotransmitter systems from the brainstem, limbic system, and other areas of the hypothalamus convey information to GnRH neurons (Kordon et al., 1994). These afferent systems include neurons that contain neurotransmitters that are generally stimulatory to GnRH neurons, such as norepinephrine, dopamine, serotonin, glutamate, neuropeptide Y, and galanin, as well as neurotransmitters that are generally inhibitory to GnRH neurons, such as gamma aminobutyric acid (GABA), endogenous opiate peptides, and the central hypothalamic hormone that governs the adrenal axis, corticotropin-releasing hormone (CRH). Importantly, both in normal physiological conditions and in response to environmental signals (such as changes in nutrition, exercise, and psychosocial stress) the activity of the reproductive axis is changed by modulation of the neural inputs into GnRH neurons. For example, various forms of stress can lead to a suppression of reproductive function by acting to increase inhibitory drive to GnRH neurons by increasing either ß-endorphin or CRH input into the GnRH neuronal system (Feng et al., 1991; Norman and Smith, 1992). Decreased firing of GnRH neurons leads to less GnRH stimulation of pituitary LH and FSH release and thus less stimulation of ovarian and testicular function. It is also important to understand that changes in neuronal function in a number of neurological and psychiatric diseases can be associated with alterations in both reproductive physiology and behavior. For example, changes in both reproductive function and sexual behavior are commonly reported by patients suffering from depression, anxiety disorders, and obsessive-compulsive disorders (Clayton, 2002; Shabsigh et al., 2001). The



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