Chapter 521

The anterior pituitary is crucial for normal growth, sexual maturation, and endocrine function. The pituitary integrates, mediates, and modulates the influence of the brain and the hypothalamus on the endocrine system (Fig. 521-1). The hypothalamus regulates anterior pituitary function by synthesizing and secreting small peptides that either promote or inhibit pituitary hormone secretion. These include growth-hormone releasing hormone (GHRH), somatostatin, thyrotropin-releasing hormone (TRH), corticotrophin-releasing hormone (CRH), and gonadotropin-releasing hormone (GnRH). Release of these factors is controlled in part by central nervous system neurotransmitters such as dopamine, norepinephrine, serotonin, and endogenous opioids. These neuropeptides are carried through the hypothalamic-hypophyseal portal circulation to anterior pituitary cells, where they bind membranous receptors and elicit intracellular cascades of activity that lead to release of the specific pituitary hormones. Pituitary hormones can modulate their own secretion by affecting the secretion of hypothalamic peptides or by acting directly on the anterior pituitary gland. These phenomena are called short and ultra-short feedback loops, respectively. The peripheral endocrine glands, whose secretion of hormones is stimulated by pituitary trophic hormones, also exert negative feedback on anterior pituitary function at the level of the hypothalamus, the pituitary gland, or both. Through these exquisitely sensitive and complex interactions, the anterior pituitary gland regulates much of the endocrine milieu of the body.

###### Figure 521-1.

Brain-hypothalamic-pituitary-target organ axis. This schema depicts the complex regulatory interrelations among brain neurotransmitters and peptides, hypothalamic releasing and inhibiting factors, pituitary trophic hormones, and target organ hormones. Arrows indicate the avenues of regulation. Signs (+ or –) indicate whether the effect is stimulatory or inhibitory, respectively. Negative feedback of target gland hormones is illustrated by the arrows on the left. The short and ultra-short-loop negative feedback mechanism is illustrated on the right by the inhibitory effects of trophic hormones on secretions from the hypothalamus and anterior pituitary, respectively.

### Embryology and Development

The anterior pituitary gland is derived from invagination of ectodermal cells in the roof of the primitive oral cavity (stomodeal ectoderm), whereas the posterior pituitary gland (neurohypophysis) is derived from neural cells in the floor of the third ventricle. A group of homeobox genes encode multiple intracellular transcription factors and extracellular signaling peptides that direct temporal and anatomic development of the pituitary.1,2 The developing pituitary and hypothalamus are in close proximity, and their embryogenesis is codependent.

The pituitary is connected to the hypothalamus by a stalk and is separated from the brain by a reflection of the dura mater (Fig. 521-2). The hypothalamic-releasing and hypothalamic-inhibiting factors reach the anterior pituitary gland through the hypothalamic-hypophyseal portal circulation. At its source in the floor of the hypothalamus, this vascular system is a dense network of arterioles and capillaries. In the pituitary stalk, it is composed of portal veins that drain into sinusoidal capillaries in the anterior pituitary gland. Arterial blood derived from branches ...

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