Hypothalamic Pituitary Axis

The hypothalamus affects several nonendocrine functions, including appetite, sleep, body temperature, and activity of the autonomic nervous system. In addition, the hypothalamus modulates the pituitary hormone secretions. The pituitary gland is often referred to as the "master gland" in recognition of its role in orchestrating the hormonal secretions of the other endocrine glands (Mooradian and Kore-nman, 2007; Mooradian and Morley, 1988). The pituitary gland is located in the anterior fossa, in the sella turcica, close to the optic chiasm. The pituitary is composed of the adenohypophysis, or anterior lobe, and the neurohypophy-sis, or posterior lobe, and is connected to the hypothalamus by the pituitary stalk.

The hormonal secretions of the anterior pituitary (the adenohypophysis) are regulated by a number of hypothalamic releasing hormones and inhibitory molecules. These factors reach the pituitary through the portal circulation and, on interaction with specific receptors, either stimulate or inhibit the secretion of the anterior pituitary hormones. The main releasing hormones include thyrotropin-releasing hormone (TRH), gonadotropin-releasing hormone (GnRH), cortico-tropin-releasing hormone (CRH), and growth hormone-releasing hormone (GHRH). The two major inhibitory factors are dopamine, which principally inhibits prolactin release, and somatostatin, a potent inhibitor of growth hormone (GH), and to a lesser extent, thyrotropin (TSH). Other factors have an important regulatory effect on anterior pituitary function. The kisspeptin hormones are a family of peptides encoded by the KiSS-1 gene and are thought to play a critical role in reproduction. Kisspeptin receptors stimulate GnRH release and activation of the mammalian reproductive axis. Mutations in kisspeptin receptor GPR-54 cause idiopathic hypogonadotropic hypogonadism, characterized by delayed or absent puberty (Jayasena and Dhillo, 2009).

The portal circulation also allows pituitary hormones to flow backward to the hypothalamus and provide feedback on their own releasing hormones to create a short-loop regulatory system. The control of the pituitary hormonal secretion is the result of interplay between the effects of hypothalamic releasing hormones and the long-loop negative feedback on the pituitary and hypothalamus by hormones secreted by endocrine glands in the periphery. For example, a rise in plasma thyroid hormone level "feeds back" and suppresses pituitary TSH and hypothalamic TRH secretion.

The posterior lobe (pars nervosa) of the pituitary is essentially an extension of the hypothalamus where the nerve endings, originating in the paraventricular and supraoptic nuclei, project as the supraopticohypophyseal tract. The posterior pituitary hormones vasopressin and oxytocin are directly controlled by neural impulses and are released into the inferior hypophyseal veins and then into the systemic circulation (Mooradian and Morley, 1988).

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