Chapter 20. Pituitary Gland & Hypothalamus

This chapter should help the student to:

• Describe the location and embryonic origins of the pituitary gland.
• Name the divisions of the pituitary gland and describe their location.
• Name the cell types in each pituitary division and indicate any characteristic staining properties.
• List the pituitary hormones, indicating for each the division and cell type of origin, and the target of the hormone.
• Describe the role of the hypothalamus in controlling pituitary gland function.
• Describe the blood supply to the pituitary gland and its role in pituitary function.
• Explain the role of negative feedback in pituitary gland function.
• Distinguish between the neurohypophysis and the adenohypophysis and identify their subdivisions, sinusoids, and cell types in a micrograph of the pituitary gland.

1. Describe endocrine gland characteristics in terms of embryonic origin (I.B), secretory cell arrangement (I.C), abundance of blood capillaries (I.C), mode of secretion release and transport (I.D), and typical secretory product (I.D).

2. Describe hormones in terms of:

1. Chemical composition (two basic types; I.D.1 and 2)

2. Relative distance and the route between the secretory cell and the target site (I.D)

3. Relative amount needed to elicit a response from the target cell (I.D)

4. General function (I.D)

3. Describe the location of the pituitary gland (hypophysis) and its relations to the hypothalamus, sella turcica, and optic chiasm (II).

4. Name the pituitary gland's two major divisions (Table 20–1) and compare them in terms of:

1. Embryonic origin

2. Microscopic structure

3. Hypothalamic connections (vascular versus neural; III.F; IV.D; Fig. 20–2)

4. Major hormones released (III.A.2.a and b; IV.A.1; Table 20–1)

5. Sketch the adult pituitary gland and hypothalamus and label the following (Fig. 20–2):

1. Adenohypophysis

2. Neurohypophysis

3. Hypothalamus

4. Anterior lobe

5. Posterior lobe

6. Optic chiasm

7. Pars distalis

8. Pars tuberalis

9. Pars intermedia

10. Rathke's cysts

11. Median eminence

12. Infundibulum

13. Pars nervosa

14. Supraoptic nucleus

15. Paraventricular nucleus

16. Primary capillary plexus

17. Secondary capillary plexus

18. Hypophyseal portal veins

6. Name the three major subdivisions of the adenohypophysis (Table 20–1).

7. Name the parenchymal cell types in the adenohypophysis, based on their staining properties (III.A.1, 2.a and b).

8. Compare pituitary acidophils and basophils (III.A.2.a and b; Table 20–2) in terms of:

1. Staining properties, including:

   1. Affinity for acidic dyes (e.g., eosin)

   2. Affinity for basic dye (e.g., hematoxylin)

   3. PAS staining

2. Hormones secreted by each cell type

9. Name the primary target organs of (and response to) the following hormones (Table 20–2):

1. FSH

2. LH

3. ICSH

4. TSH

5. Growth hormone

6. Prolactin

7. ACTH

10. Beginning with neural stimulation of the hypothalamus, trace the events leading to thyroid hormone secretion (T3 and T4) by the thyroid gland. Name, in order, the neural, endocrine, and vascular components involved (III.A.2.b and E; Table 20–2).

11. Name the major subdivisions of the neurohypophysis (Table 20–1).

12. Where are the cell bodies of the pars nervosa's unmyelinated axons located (IV.A)?

13. Describe Herring bodies in terms of their contents, appearance, and location (IV.A).

14. List the contents of the neurosecretory vesicles in the axons of the pars nervosa (IV.A.1–3).

15. Describe pituicytes in terms of structure and function (IV.C).

16. Name the two major neurohypophyseal hormones, their target organs, and the effects they elicit (IV.A.1; Table 20–2).

I. General Features of the Endocrine System

A. Components of the System

The endocrine system includes several organs (e.g., adenohypophysis, thyroid gland, adrenal gland), islands of endocrine tissue in exocrine glands (e.g., islets of Langerhans), and some isolated endocrine cells (e.g., cells with DNES functions in the digestive tract mucosa).

B. Origin

Endocrine glands are ductless glands that develop as invaginations of epithelial surfaces, such as oral ectoderm or gut endoderm, and subsequently pinch off, losing contact with the parent epithelium.

C. Microscopic Structure

Endocrine glands typically contain secretory cells arranged as cords, clumps, or follicles in direct contact with abundant capillaries or sinusoids.

D. Secretions

Endocrine cells release their secretions—typically hormones—into the bloodstream. Other products released into the bloodstream rather than into ducts (e.g., enzymes, serum albumin) are also considered endocrine secretions. Hormones are molecules with specific regulatory effects on a target cell, tissue, or organ that is often located far from the gland. Hormones elicit specific and dramatic effects at very low concentrations. They directly or indirectly affect all tissues and many are essential to maintaining the internal steady-state environment. They regulate carbohydrate, protein, and lipid metabolism; mineral and water balance in body fluids; growth; sex-related differences in body shape and sexual function; and behavior, temperament, and emotions.

1. Peptide hormones. These proteins, glycoproteins, or short peptides bind to specific receptors on target cell surfaces. They often stimulate the production of intracellular second messengers, such as cyclic AMP, in the target cells (2.II.C.2).

2. Steroid hormones. These lipid-soluble hormones easily cross target cell plasma membranes to directly affect cell function. They bind to specific binding proteins in the cytoplasm and the nucleus. The nuclear receptors subsequently bind to DNA and directly affect gene transcription.

E. Neuroendocrine System

The complex, interrelated functions of cells, tissues, and organs are controlled and coordinated by two overlapping systems: the nervous system (Chapter 9) and the endocrine system (Chapters 20, 21, 22, 23). Increasingly, these are considered parts of a single neuroendocrine system. Once called the master gland because of its ability to control other glands, the pituitary gland (hypophysis) currently is seen as a focal connection between the endocrine and nervous systems. The secretory activities of its two parts, the adenohypophysis and the neurohypophysis, are both controlled by a nearby part of the brain, the hypothalamus. Hypothalamic activity is controlled by neural connections with other parts of the nervous system and by negative feedback from the hormones produced by the pituitary gland's target cells. Pituitary-related diseases present chiefly as the effects of hypersecretion or hyposecretion of pituitary hormones; they may be caused by lesions of the pituitary gland, its target organs, or the hypothalamus.

II. Location, General Organization, & Embryonic Origins of the Pituitary Gland

The pituitary gland is suspended by a stalk from the hypothalamus at the base of the diencephalon. It rests in a depression in the sphenoid bone called the sella turcica, behind the optic chiasm. Its two major divisions, the anterior adenohypophysis and the posterior neurohypophysis, differ in embryonic origin (Fig. 20–1), structure, and function (Tables 20–1 and 20–2).

III. Adenohypophysis

Each secretory cell in the adenohypophysis synthesizes and stores one of the following hormones: follicle-stimulating hormone (FSH), thyrotropin (thyroid-stimulating hormone [TSH]), luteinizing hormone (LH), adrenocorticotropic hormone (ACTH), growth hormone (GH), or prolactin. These hormones control the secretory activities of many other glands. Their release is regulated by specific releasing or inhibiting hormones produced by the hypothalamus and delivered to the adenohypophysis by the blood in the hypophyseal portal system (III.D).

A. Pars Distalis

1. Chromophobes. These cells stain poorly and appear clear or white in tissue sections. Together, the three chromophobe subpopulations make up approximately 50% of the pars anterior's epithelial cells. They include (1) undifferentiated nonsecretory cells, which may be stem cells; (2) partly degranulated chromophils, which contain sparse granules; and (3) follicular cells, the predominant chromophobe type, which form a stromal network supporting the chromophils; these stellate cells may be phagocytic.

2. Chromophils. These hormone-secreting cells stain intensely, owing to the abundant cytoplasmic secretory granules in which hormones are stored. A specific cell type exists for each hormone. Usually larger than chromophobes, chromophils comprise two classes:

   1. Acidophils secrete simple proteins and stain intensely with eosin but respond negatively to the PAS reaction. More abundant in the gland periphery, they are usually smaller than basophils and have larger and more numerous granules. The acidophils include two major hormone-secreting cell types: somatotrophs produce GH, (somatotropin) and mammotrophs produce prolactin. (A mnemonic for hormones secreted by acidophils is GPA: growth hormone, prolactin, acidophils.)

   2. Basophils secrete glycoproteins, stain with hematoxylin and other basic dyes, and respond positively to the PAS reaction. More abundant in the core of the gland, they are usually larger than acidophils, with fewer and smaller granules. The three major hormone- producing basophils produce four major hormones. (A mnemonic for hormones produced by basophils is B-FLAT: basophils, FSH, LH, ACTH, TSH.) Each of the two gonadotrophs produces a different gonadotropin. One produces FSH; the other produces LH. Corticotrophs produce adrenocorticotropin (ACTH). Thyrotrophs produce thyrotropin (TSH).

B. Pars Tuberalis

This funnel-shaped superior extension of the pars distalis surrounds the infundibular stem (Fig. 20–2). It resembles the pars distalis but contains mostly gonadotrophs. The pars tuberalis contains many capillaries of the primary capillary plexus (III.D.1).

C. Pars Intermedia

This is a band or wedge of adenohypophysis between the pars distalis and pars nervosa; it is rudimentary in humans. It contains Rathke's cysts—small, irregular, colloid-containing cavities lined with cuboidal epithelium that are the remnants of Rathke's pouch. It also contains scattered clumps and cords of basophilic cells, or melanotrophs, which secrete melanocyte-stimulating hormone (β-MSH).

D. Blood Supply and Hypophyseal Portal System

1. Primary capillary plexus. This profusion of capillaries lies in the upper infundibular stalk and lower median eminence; it extends into the pars tuberalis (see Fig. 20–2). The plexus receives blood from the anterior and posterior superior hypophyseal arteries (from the circle of Willis) and drains into the hypophyseal portal veins.

2. Hypophyseal portal veins. These small veins and venules lie mainly in the middle and lower infundibular stalk and in parts of the pars tuberalis. They receive blood from the primary capillary plexus and carry it directly to the secondary capillary plexus in the pars distalis (see Fig. 20–2). Vessels carrying blood directly from one capillary plexus to another without returning to the general circulation are defined as portal vessels.

3. Secondary capillary plexus. This rich plexus of fenestrated capillaries and sinusoids throughout the pars distalis also penetrates the pars tuberalis and pars intermedia (see Fig. 20–2). Some connections exist between this capillary bed and that in the pars nervosa. The sinusoids between the clumps and cords of cells in the pars distalis belong to this plexus, which receives venous blood directly from the hypophyseal portal veins and arterial blood from the anterior inferior hypophyseal arteries. It is drained by the inferior hypophyseal veins into the internal jugulars.

E. Hypothalamic Releasing and Inhibiting Hormones

These small peptides are synthesized in the neuron (neurosecretory) cell bodies of the hypothalamic nuclei and are released by their axon terminals around the primary capillary plexus. They pass through the hypophyseal portal venules and into the secondary capillary plexus, from which they diffuse into the adenohypophysis to stimulate or inhibit the hormone release by acidophils and basophils.

1. Releasing hormones. Corticotropin-releasing hormone (CRH) is a 41-amino-acid peptide synthesized in the paraventricular nucleus; it stimulates corticotrophs to release ACTH. Gonadotropin-releasing hormone (GnRH), a 10-amino-acid peptide synthesized in the preoptic and arcuate nuclei, stimulates gonadotrophs to release FSH and LH. Thyrotropin-releasing hormone (TRH) is a 3-amino-acid peptide that stimulates thyrotrophs to release TSH (thyrotropin).

2. Inhibiting hormones. Somatostatin (growth hormone–inhibiting hormone [GHIH]) is a 14-amino-acid peptide synthesized in the suprachiasmatic nuclei that inhibits somatotrophs from releasing GH (somatotropin). It also inhibits the secretion of glucagon, insulin, and other hormones associated with the gastrointestinal tract. Dopamine (a prolactin-inhibiting hormone [PIH]) is a neurotransmitter synthesized in the arcuate nuclei that inhibits prolactin release from mammotrophs.

F. Summary of Adenohypophyseal Hormone Production

1. Neurons of the hypothalamic nuclei synthesize releasing or inhibiting hormones and package them in neurosecretory vesicles.

2. The neurons transport the vesicles down the axons in the tuberoinfundibular and hypothalamohypophyseal tracts, where they collect in the axon terminals surrounding capillaries of the primary plexus.

3. Neural stimulation or hormonal feedback from target organs of the adenohypophysis causes the nerves of the tuberoinfundibular and hypothalamohypophyseal tracts to fire an action potential that releases the appropriate releasing or inhibiting hormone from their axon terminals.

4. The releasing or inhibiting hormone enters the primary capillary plexus and flows through the hypophyseal portal veins to the secondary capillary plexus.

5. Here, the hormone diffuses out of the capillary lumen by means of the fenestrae and stimulates or inhibits the release of stored adenohypophyseal hormones from the acidophils or basophils.

6. The adenohypophyseal hormones enter the capillaries of the secondary plexus; they leave the adenohypophysis through the anterior inferior hypophyseal veins to enter the general circulation.

IV. Neurohypophysis

The subdivisions of the neurohypophysis (outlined in Table 20–1)—all exhibit similar microscopic structure. For brevity, the pars nervosa is used here to represent the neurohypophysis. The neurohypophysis has three major structural components: axons, capillaries, and pituicytes.

A. Axons of Neurosecretory Cells

The neurohypophysis stains poorly. It contains many unmyelinated axons whose cell bodies (soma) lie mainly in the supraoptic and paraventricular nuclei (see Fig. 20–2) of the hypothalamus. Axons passing from these nuclei to the pars nervosa together comprise the hypothalamohypophyseal tract. These axons contain neurosecretory granules and have large granule-filled dilations called Herring bodies. The neurosecretory materials in these granules, synthesized and packaged in the cell bodies, include the following products:

1. Neurohypophyseal hormones. The hypothalamic neurons terminating in the neurohypophysis release oxytocin and antidiuretic hormone (ADH) around the capillaries in this part of the pituitary gland. Oxytocin is a 9-amino-acid peptide synthesized mainly by cells of the paraventricular nucleus. It stimulates milk ejection by the mammary glands and also stimulates uterine smooth muscle contraction during copulation and childbirth. ADH (arginine vasopressin) is a 9-amino-acid peptide synthesized mainly by cells in the supraoptic nucleus. It stimulates water reabsorption by the renal medullary collecting ducts (19.II.C.2) and the contraction of vascular smooth muscle.

2. Neurophysins are binding proteins that complex with neurohypophyseal hormones.

3. Adenosine triphosphate (ATP) acts as a chemical energy source for neurosecretion.

B. Fenestrated Capillary Plexus

Surrounding the axon terminals in the pars nervosa, these capillaries deliver neurosecretory products to the general circulation.

C. Pituicytes

These are highly branched glial cells whose processes surround and support the unmyelinated axons. Their nuclei are typically larger and more euchromatic than those of the many neural-crest-derived fibroblasts in this tissue.

D. Summary of Neurohypophyseal Hormone Production

Neurons of the supraoptic and paraventricular nuclei of the hypothalamus synthesize ADH and oxytocin, respectively. The neurons package these hormones with neurophysins and ATP in neurosecretory vesicles. The vesicles are transported by the neurons down the axons in the hypothalamohypophyseal tract to axon terminals among the capillaries of the pars nervosa. In response to appropriate stimulation, these neurosecretory cells propagate an action potential along their axons, causing exocytosis of the vesicle contents at the axon terminals. The released hormones enter the capillaries of the pars nervosa and leave the pituitary gland to enter the general circulation by means of the posterior inferior hypophyseal veins.