Normal Hypothalamic Pituitary Axis

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The hypothalamic-pituitary axis (HPA) is the primary interface between the nervous system and the endocrine system. The actions and interactions of the endocrine and nervous systems constitute the major regulatory mechanisms for virtually all physiologic functions. The hypothalamus has extensive neural communications with other brain regions and regulates brain functions, including temperature, appetite, thirst, sexual behavior, and fear. The hypothalamus also contains two types of neurosecretory cells (Fig. 5.1): (1) neurohypophysial neurons, which transverse the hypothalamic-pituitary stalk and release vasopressin and oxytocin from their nerve endings in the posterior pituitary, and (2) hypophys-iotropic neurons, which release hormones into the portal hypophysial vessels to regulate the secretion of tropic hormones from the anterior pituitary. The six anterior pituitary hormones and their major hypothalamic regulatory factors are listed in Table 5.1.

Diagrammatic Representation Pituitary

Diagrammatic representation of the hypothalamic-pituitary axis

Figure 5.1

Diagrammatic representation of the hypothalamic-pituitary axis

5.1.1.1 Growth Hormone

Growth hormone (GH) is a 191-amino acid polypeptide synthesized and secreted by the somatotrophs in the anterior pituitary gland in response to the hypothalamus releasing hormones, primarily GH-releasing hormone (GHRH) and somatostatin. GHRH secretion is usually steady, whereas somatostatin secretion is interrupted intermittently. Somatostatin contributes to the synthesis of GH in the pituitary but, paradoxically, inhibits GH release [45]. When somatostatin concentrations decrease, the tonic concentration of GHRH causes the release of GH into the systemic circulation. Factors such as neuropeptide Y, leptin, galanin, and ghrelin may also regulate GH secretion. In healthy children and adults, GH secretion is pulsatile, particularly during sleep,with two to six pulses per night [50]. In adolescents, additional pulses occur during the day, and the pulses have higher peaks than those seen in children and adults (Fig. 5.2 a).

Circulating serum GH stimulates the production of insulin-like growth factor I (IGF-I) in all tissues. IGF-I mediates GH effects on growth, bone mineralization, and body composition (decreased fat deposition, increased muscle mass) [71]. IGF-I is bound to IGF-binding proteins such as IGFBP3 and is transported in the blood. IGF-I and IGFBP3 concentrations are stable during the day and each reflects the integrated concentration of secreted GH.

5.1.1.2 Gonadotropins

Luteinizing hormone (LH) and follicle stimulating hormone (FSH) are glycoproteins both stored in the same cells in the anterior pituitary. Their overall patterns of secretion vary according to the age and gender of the person. The pituitary gland produces and secretes LH and FSH in a pulsatile manner in response to a concordant episodic release of gonado-tropin-releasing hormone (GnRH) from the hypothalamus (Fig. 5.2a). The hypothalamic stimulus is actively inhibited between 6 months of age and the onset of puberty (Fig. 5.2b). This inhibition can be disturbed by tumor mass, cranial surgery, or irradiation, thereby resulting in precocious puberty in chil

Precocious Puberty Pituitary

Figure 5.2 a,b a Changes with pubertal status in the normal daily pattern of growth hormone (GH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), and adreno-corticotropin (ACTH) and cortisol secretion. b Normal changes in LH and FSH levels from infancy to adolescence

Figure 5.2 a,b a Changes with pubertal status in the normal daily pattern of growth hormone (GH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), and adreno-corticotropin (ACTH) and cortisol secretion. b Normal changes in LH and FSH levels from infancy to adolescence dren. In men, LH stimulates testosterone production in the Leydig cells of the testes; normal spermatogen-esis requires both LH and FSH. In women, FSH stimulates the production of estrogen and LH stimulates the production of progesterone in the ovary. The LH surge near the end of the follicular phase of the menstrual cycle is necessary to stimulate ovulation. Development of the ovarian follicles is largely under a b

FSH control, and the secretion of estrogen from the follicle is dependent on both FSH and LH (see section 5.2.2 for information on the normal development of the gonads).

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