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The pituitary gland


Introduction

The hypothalamus and pituitary gland constitute an elegant center of hormonal control known as the hypothalamic-pituitary axis (HPA).

  • Each hormone controlled by the pituitary is regulated separately along its own pathway, or “axis.”

  • The HPA integrates information from the body’s internal and external environments with higher cortical input.

  • The HPA then orchestrates changes in the multiple physiologic systems controlled by the pituitary hormone axes, allowing for coordinated hormonal responses to stimuli.

    • Necessary for daily activities (i.e., eating, sleeping), but also for efficient response to illness and other physiologic stress.

Pituitary hormones act on both endocrine and nonendocrine sites, including the kidneys, adrenal glands, thyroid, ovaries, testes, breast, uterus, and vascular smooth muscle. These hormones are essential to metabolic and autonomic nervous system function and also support changes that occur throughout life.

System structure

The pituitary gland (or hypophysis, meaning “undergrowth”) is a small endocrine gland (0.5–0.9 g). The pituitary gland is located below the hypothalamus, attached to it by the pituitary infundibulum, or neural stalk ( Fig. 29.1 ).

  • The pituitary rests in the sella turcica (Latin for “Turkish saddle”) of the sphenoid bone.

  • It is separated from the brain and its surrounding arachnoid membranes and cerebrospinal fluid by a reflection of the dura mater called the diaphragmatic sellae.

  • The pituitary is inferior and slightly posterior to the optic chiasm.

  • It lies posterior to the air-filled sphenoid sinus and adjacent to the venous cavernous sinuses through which travel cranial nerves III, IV, and VI and the internal carotid artery.

  • Any of these anatomic structures may be compressed and disturbed by pituitary tumors (see Clinical Correlation Box 29.1 ).

Fig. 29.1, Midsagittal cross-section of the hypothalamus. The infundibulum connects the pituitary with the hypothalamus.

Clinical Correlation Box 29.1

Surgeons often reach the pituitary through a transnasal approach via the sphenoid sinus. Surgical equipment is inserted up the nasal cavity and through the sphenoid bone, giving access to the cranium.

Gross anatomy

The pituitary has three divisions, the most important of which are the anterior and posterior lobes ( Fig. 29.2 ):

  • Anterior lobe (adenohypophysis)

    • Synthesizes and secretes six hormones ( Table 29.1 )

      • Adrenocorticotropic hormone (ACTH)

      • Thyroid-stimulating hormone (TSH)

      • Growth hormone (GH)

      • Follicle-stimulating hormone (FSH)

      • Luteinizing hormone (LH)

      • Prolactin

      TABLE 29.1
      Pituitary Hormones
      Compound Size (kDa) Structure End Organ
      Anterior Pituitary
      ACTH MW 4500 39 aa a Adrenal cortex
      TSH Glycoprotein
      MW 28,000       		alpha subunit b : 89 aa
      beta subunit: 112 aa       		Thyroid
      GH MW 21,500 191 aa polypeptide IGF-1 production; growth and metabolic effects
      FSH Glycoprotein
      MW 29,000       		alpha subunit b : 89 aa
      beta subunit: 115 aa       		Ovaries
      Testes
      LH Glycoprotein
      MW 29,000       		alpha subunit b : 89 aa
      beta subunit: 115 aa       		Ovaries
      Testes
      Prolactin MW 22,000 198 aa polypeptide Breast
      Posterior Pituitary
      ADH Nonapeptide (9 aa) Vascular smooth muscle; distal tubule of kidney
      Oxytocin Nonapeptide (9 aa) Mammary gland smooth muscle; uterus
      ACTH , Adrenocorticotropic hormone; ADH , antidiuretic hormone; FSH , follicle-stimulating hormone; GH , growth hormone; IGF-1 , insulin-like growth factor-1; LH , luteinizing hormone; MW , molecular weight; TSH , thyroid-stimulating hormone.

      a aa, amino acid.

      b The alpha subunits of TSH, FSH, and LH, as well as hCG (human chorionic gonadotropin, a compound released by the placenta), are identical; the beta subunits are distinct and give each its identity and function.

  • Posterior lobe (neurohypophysis)

    • Stores and releases two hormones (see Table 29.1 ):

      • Antidiuretic hormone (ADH)

      • Oxytocin

  • Infundibulum

    • Stalk-like structure that connects the pituitary to the hypothalamus.

    • Consists of the more proximal median eminence and the distal stalk.

    • Contains vasculature carrying hypothalamic hormones to the anterior pituitary and neural tracts that project from the hypothalamus to the posterior lobe.

Fig. 29.2, Anterior and posterior pituitary. The posterior pituitary comprises axonal projections from cell bodies in the hypothalamic nuclei. Both anterior and posterior pituitary cells secrete hormones into a capillary plexus supplied by the hypophyseal arteries and the pituitary portal circulation, bringing blood from the hypothalamus.

Histology of the anterior lobe

The anterior lobe consists of cords of secretory cells, fibroblasts, and capillary endothelial cells. The secretory cells are named according to the staining properties of their granules:

  • Chromophils

    • Acidophils

    • Basophils

  • Chromophobes

    • Few or no secretory granules.

    • May represent undifferentiated chromophils, or chromophils that have released their granules.

The acidophils and basophils are further classified on the basis of the hormones they produce ( Table 29.2 ):

  • Acidophils

    • Somatotrophs (GH)

    • Lactotrophs (Prolactin)

  • Basophils

    • Corticotrophs (ACTH)

    • Thyrotrophs (TSH)

    • Gonadotrophs (FSH, LH)

TABLE 29.2
Anterior Lobe Cell Types
Cell Type (% of Anterior Lobe Cells) Staining Properties Secretory Granules (nm) Hormone Product(s)
Somatotroph (50) Acidophilic 300–400 GH (somatotropin)
Lactotroph (mammotroph) (10–25) Acidophilic 200 (600 in pregnant or lactating women) Prolactin
Corticotroph (15–20) Basophilic 400–550 ACTH a (corticotropin)
Thyrotroph (<10) Basophilic 120–200 TSH (thyrotropin)
Gonadotroph (10–15) Basophilic 250–400 FSH, LH
ACTH , Adrenocorticotropic hormone; FSH , follicle-stimulating hormone; GH , growth hormone; LH , luteinizing hormone.

a Corticotrophs synthesize and releases multiple peptides; see text.

The anterior pituitary depends on stimulating factors from the parvocellular (small-diameter) neurons of the hypothalamus.

  • The axons of these neurons release substances into the fenestrated capillaries of the median eminence.

  • These capillaries coalesce into hypophyseal portal vessels that travel down the infundibulum, form another capillary bed, and release substances to the anterior pituitary.

  • This is known as the pituitary portal circulation (see Clinical Correlation Box 29.2 ).

Clinical Correlation Box 29.2
Portal Circulations

In the systemic circulation, the vascular sequence is arteries → capillaries → veins. In a portal circulation, such as in the pituitary or the liver, there is an additional set of veins and capillaries, yielding the sequence arteries → capillaries → veins → capillaries (or venules) → veins. A portal system is used to transport substances in a focused, undiluted fashion to a site for a specific purpose, such as detoxification (liver) or hormonal signaling (pituitary).

Histology of the posterior lobe

The posterior lobe contains the unmyelinated axons of hypothalamic neurosecretory cells, pituicytes (specialized glial cells), and capillary endothelial cells.

  • No hormone synthesis occurs in the posterior lobe.

Magnocellular (large-diameter) hypothalamic neurons originate in the paraventricular and supraoptic nuclei.

  • Their axons carry hormones down the infundibulum into the posterior lobe, where they are stored.

  • The axon terminals are adjacent to fenestrated capillaries and release hormones directly to the systemic circulation without making use of the pituitary portal circulation.

System function

As previously mentioned, each pituitary hormone is controlled by a corresponding HPA. Each axis has several factors modulating its activity, including:

  • Primary regulatory agents (major)

  • Regulatory agents of other HPAs

    • In other words, pathology in one axis can readily disrupt others.

  • Changes in body metabolism or electrolyte balance

  • Higher cortical input

The primary control mechanisms include ( Fig. 29.3 ):

  • Hypothalamic releasing factors

    • A positive releasing factor stimulates the release of a compound, whereas a negative factor inhibits its release.

    • All the hypothalamic regulatory hormones are peptides, except dopamine, which is a biogenic amine.

    • Most hypothalamic and pituitary hormones are secreted in bursts, known as pulsatility.

  • Feedback loops

    • Definition: the end-product of a chain of events feeds back to an earlier step.

      • If the effect is inhibitory, this is called negative feedback.

      • If the effect is stimulatory, this is called positive feedback.

    • Negative feedback is more common because it prevents the overproduction of a compound; when a sufficient amount of a hormone has been produced, it shuts off its own releasing process.

    • Example: Hypothalamic thyrotropin-releasing hormone (TRH) prompts TSH from the pituitary gland, which leads to thyroid hormone release from the thyroid; this subsequently inhibits both TRH and TSH.

Fig. 29.3, Actions of pituitary hormones on target tissues. ACTH , Adrenocorticotropic hormone; FSH , follicle-stimulating hormone; LH , luteinizing hormone; TSH , thyroid-stimulating hormone

The pituitary gland also provides the basis for adaptations at various life-cycle stages or during a chronic illness.

  • In these settings, significant changes in pituitary hormones and the systems they regulate are made possible by changes in gland size.

  • During pregnancy, for example, lactotroph hyperplasia occurs to provide a needed increase in prolactin.

The anterior pituitary

The six hormones synthesized in the anterior pituitary (ACTH, TSH, GH, FSH, LH, and prolactin) individually affect the activity of one or more target organs ( Fig. 29.4 ). They are under the influence of several hypothalamic regulatory factors:

  • Corticotropin-releasing hormone (CRH)

  • TRH

  • Growth hormone-releasing hormone (GHRH)

  • Gonadotropin-releasing hormone (GnRH)

  • Hypothalamic inhibitory factors

  • Somatostatin

  • Prolactin-inhibiting factor (PIF)

Fig. 29.4, Hypothalamic-pituitary-adrenal axis. Plus signs represent stimulation; minus signs represent inhibition. ACTH , Adrenocorticotropic hormone; CRH , corticotropin-releasing hormone.

The roles of these regulatory factors are summarized in Table 29.3 .

TABLE 29.3
Hypothalamic Regulatory Hormones
Hypothalamic Hormone Structure Function a
Thyrotropin-releasing hormone (TRH) Tripeptide (3 aa b ) Stimulates TSH release by thyrotroph; stimulates prolactin release by lactotroph
Corticotropin-releasing hormone (CRH) 41 aa polypeptide Stimulates ACTH release by corticotroph
Gonadotropin-releasing hormone (GnRH) Decapeptide (10 aa) Stimulates FSH and LH release by gonadotroph
Growth hormone-releasing hormone (GHRH) 44 aa polypeptide Stimulates GHRH release by somatotroph
Somatostatin 14 aa peptide Inhibits GH release by somatotroph; inhibits TSH release by thyrotroph
Prolactin-inhibiting factor (PIF) Dopamine c Inhibits prolactin release from lactotroph
ACTH , Adrenocorticotropic hormone; FSH , follicle-stimulating hormone; GH , growth hormone; LH , luteinizing hormone; TSH , thyroid-stimulating hormone.

a Primary function. Almost all hypothalamic hormones have some effects on each of the anterior pituitary cell types.

b aa, amino acid.

c Evidence indicates that there may be additional PIFs. However, dopamine appears to be the primary PIF.

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