24.1 Interaction between the Hypothalamus and Pituitary
The hypothalamus and pituitary constitute a functional unit that represents the greatest integration of central nervous system control of endocrine systems.
Hypothalamic–Anterior Pituitary Axis
Hypothalamic neuropeptide hormones regulate the biosynthesis and release of hormones from the anterior pituitary. They are synthesized in hypothalamic neurons whose axons terminate at a primary capillary plexus. Upon stimulation, these neuropeptide hormones are released into the capillary bed, where they travel quickly to the anterior pituitary via the hypothalamichypophysial portal system. This terminates at a second, highly fenestrated capillary bed in the anterior pituitary, where they are free to diffuse into the extracellular fluid bathing the anterior pituitary cells. This bed drains into the cavernous sinus and jugular vein, allowing for the peripheral transport of any released anterior pituitary hormones (Fig. 24.1).
Hypothalamic–Posterior Pituitary Axis
The posterior pituitary contains axons whose cell bodies are located in the hypothalamic nuclei (paraventricular nuclei and supraoptic nuclei). These neurons are much larger than those regulating the anterior pituitary. Posterior pituitary hormones are synthesized in the cell bodies in the hypothalamus and travel down the axons to be released by the posterior pituitary upon stimulation (Fig. 24.1). The posterior pituitary hormones also reach the peripheral circulation and target organs via the cavernous sinus and jugular vein.
Embryology of the hypothalamus and pituitary glands
The anterior pituitary arises from an invagi-nation of oral ectoderm (Rathke pouch). The hypothalamus and posterior pituitary are derived from neuroectoderm.
Transsphenoidal pituitary surgery
Most pituitary tumors are removed endoscopically through the sphenoid sinus, which can be accessed through the nostril. This approach provides relatively easy surgical access to the pituitary and leaves no visible scarring.
Table 24.1 provides a summary of hypothalamic and pituitary hormones.
Fig. 24.1 Hypothalamic–pituitary hormone secretion.
The hypothalamus responds to impulses from the central nervous system by releasing stimulating and/or inhibiting hormones that are carried to the pituitary via axoplasmic transport (movement through the cytoplasm of an axon). Hypothalamic hormones induce hormone release in the anterior and posterior pituitary. Hypothalamic releasing or inhibiting hormones are released into a capillary bed in the anterior pituitary. Axons from the hypothalamus terminate in the posterior pituitary to release hormones. (ACTH, adrenocorticotropic hormone; ADH, antidiuretic hormone; FSH, follicle-stimulating hormone; GH, growth hormone; IH, inhibiting hormone; LH, luteinizing hormone; MSH, melanocyte-stimulating hormone; NE, norepinephrine; NPY, neuropeptide Y; PRL, prolactin; RH, releasing hormone; TSH, thyroid-stimulating hormone)
24.2 Anterior Pituitary Hormones
Melanocyte-stimulating hormone and melanin
Melanocyte-stimulating hormone (MSH) is produced by cells in the intermediary lobe of the pituitary gland. Both MSH and adrenocorticotropic hormone (ACTH) are derived from the precursor peptide proopiomelanocortin (POMC). MSH stimulates the synthesis and secretion of melanin by melanocytes in skin and hair. It also plays a role in appetite and sexual arousal. MSH is increased in pregnancy and Cushing disease (due to increased levels of ACTH). Melanin is responsible for giving color to the hair, skin, and iris of the eyes. It also helps protect skin from sun damage by collecting in vesicles called melanosomes, which migrate to the epidermis and cover the nucleus, thus protecting DNA from damage from the sun’s ionizing radiation.
Growth hormone (GH) and prolactin have several target organs and are discussed in the following section. All remaining anterior pituitary hormones are discussed in relation to their target gland in the following chapters (Fig. 24.2).
Fig. 24.2 Effects of pituitary hormones on target tissues.
(ACTH, adrenocorticotropic hormone; ADH, antidiuretic hormone; FSH, follicle-stimulating hormone; GH, growth hormone; IGFs, insulinlike growth factors; LH, luteinizing hormone; TSH, thyroid-stimulating hormone)
Regulation of Secretion
Hypothalamic control. Growth hormone–releasing hormone (GHRH) causes increased GH synthesis and secretion.
Somatostatin, released from specific hypothalamic neurons, decreases the response of the anterior pituitary to GHRH, thus decreasing GH levels. It is identical to somatostatin secreted by the endocrine pancreas and intestinal mucosa. Somatostatin also inhibits the secretion of thyroid-stimulating hormone (TSH), ACTH, and prolactin.
Negative feedback control
– GH inhibits its own secretion by inhibiting GHRH secretion in the hypothalamus and by desensitizing the pituitary to GHRH. It also increases the secretion of somatostatin from the hypothalamus.
– Somatomedins (insulinlike growth factors [IGFs]) inhibit the secretion of GH by stimulating the secretion of somatostatin from the hypothalamus and by directly inhibiting the cells of the anterior pituitary.
Other factors. Table 24.2 lists factors that stimulate or inhibit GH secretion.
GH is essential for the growth of infants to maturity. Table 24.3 summarizes the effects of GH and somatomedins (IGFs).
Growth hormone and nitrogen balance
GH creates a positive nitrogen balance in the body. This is mainly due to an increased rate of lipolysis, which provides the energy the body needs while sparing proteins and glucose. Diseases and conditions in which there is a negative nitrogen balance, such as acquired immunodeficiency syndrome (AIDS), cachexia (loss of lean body mass that cannot be corrected with increased calorific intake), trauma, and severe burns, can be treated with GH to improve lean body mass and improve wound healing.
Growth at epiphyseal plates
The epiphyseal plate consists of hyaline cartilage at the end of long bones. Chondrocytes in the epiphyseal plates are constantly undergoing mitosis. The older cells (at the diaphysis end) are then ossified by osteoblasts. This progressive laying down of bone leads to longitudinal growth. Growth of long bones continues throughout childhood and adolescence but ceases in adulthood. GH acts to increase the mitosis of chondrocytes in the epiphyseal place and thus is ineffective for bone growth in adults.
Growth hormone deficiency. Table 24.4 summarizes some of the more common causes of GH deficiency, the symptoms produced, and treatment.
Growth hormone excess. GH excess causes gigantism in children and acromegaly in adults.
Table 24.5 summarizes the causes, symptoms, and treatment of these conditions.
The chemical structure of prolactin is closely related to that of GH.
Regulation of Secretion
Hypothalamic control. Dopamine (prolactin-inhibiting hormone [PIH]), secreted by the hypothalamus, tonically inhibits prolactin secretion. Thyrotropin-releasing hormone (TRH) increases prolactin secretion.
Negative feedback control. Prolactin inhibits its own secretion by stimulating the hypothalamus to release dopamine (via neuroendocrine reflex from the breast). It also inhibits the secretion of gonadotropin-releasing hormone (GnRH) in high concentrations.
– ↑ breast development
– ↑ milk production in the breast
– ↑ the synthesis of vitamin D3 for Ca2+ absorption
– ↓ ovulation by decreasing the synthesis and release of GnRH
– ↓ spermatogenesis by decreasing GnRH
Prolactin deficiency. Table 24.6 summarizes the causes, symptoms, and treatment of prolactin deficiency.
Prolactin excess. Table 24.7 summarizes the causes, symptoms, and treatment of prolactin excess (hyperprolactinemia).
24.3 Posterior Pituitary Hormones
Regulation of Secretion
Oxytocin secretion is stimulated by neural reflexes in response to
– breast stimulation (suckling)
– uterocervical stimulation
– emotional stimulation (e.g., sight of a neonate)
– ↑ uterine contractility involved in parturition (oxytocin receptors are upregulated during pregnancy)
– ↑ contraction of mammary myoepithelium, which results in the ejection of milk (“let-down”)
Antidiuretic Hormone (Vasopressin)
Regulation of Secretion
Regulation of ADH secretion occurs at both the neuronal soma and axonal levels. Its secretion is stimulated by the following:
– ↑ plasma osmolality (e.g., dehydration)
– ↓ plasma volume (e.g., hemorrhage, or hypovolemia)
– ↓ blood pressure (via direct effects on the baroreceptors and by decreased plasma volume)
Note: ADH release is most sensitive to plasma osmolality, yet larger quantities of ADH are released in response to major changes in blood pressure and blood volume.
Table 24.8 summarizes the effects of ADH (vasopressin) at V1 and V2 receptors.
ADH deficiency. ADH deficiency causes diabetes insipidus (summarized in Table 24.9).
ADH excess. Excess ADH release causes the syndrome of inappropriate ADH secretion (SIADH; Schwartz–Bartter syndrome). Table 24.10 summarizes this condition.