Endocrine System Part 2: Pituitary, Thyroid, Parathyroid, and Adrenal Glands

Anterior Pituitary Hormones

Overview of Anterior Pituitary Hormones

• All six anterior pituitary hormones are peptide hormones.

• All but growth hormone (GH) activate target cells via the cAMP second-messenger system.

• All but two are tropic hormones (tropins), meaning they regulate the secretion of other hormones.

• The six hormones are:

  • Growth hormone (GH)

  • Thyroid-stimulating hormone (TSH) (tropic)

  • Adrenocorticotropic hormone (ACTH) (tropic)

  • Follicle-stimulating hormone (FSH) (tropic)

  • Luteinizing hormone (LH) (tropic)

  • Prolactin (PRL)

Growth Hormone (GH)

• Also called somatotropin, produced by somatotropic cells.

• Has direct actions on metabolism and indirect growth-promoting actions.

• Direct actions on metabolism:

  • Glucose-sparing actions decrease the rate of cellular glucose uptake and metabolism (anti-insulin effects).

  • Stimulates the liver to break down glycogen into glucose.

  • Increases blood levels of fatty acids for use as fuel and encourages cellular protein synthesis.

• Indirect actions on growth:

  • GH triggers the liver, skeletal muscle, and bone to produce insulin-like growth factors (IGFs).

  • IGFs stimulate cellular uptake of nutrients for DNA and protein synthesis, and formation of collagen and bone matrix.

  • GH stimulates most cells to enlarge and divide, with major targets being bone and skeletal muscle.

• Regulation of secretion:

  • GH release/inhibition is chiefly regulated by hypothalamic hormones acting on somatotropic cells.

  • Growth hormone-releasing hormone (GHRH) stimulates GH release (triggered by low blood GH or glucose, or high amino acid levels).

  • Growth hormone-inhibiting hormone (GHIH, somatostatin) inhibits GH release (triggered by increased GH and IGF levels).

  • Ghrelin (hunger hormone) also stimulates GH release.

Clinical Considerations: GH Disorders

• Hypersecretion of GH (usually due to anterior pituitary tumor):

  • In children: gigantism (can reach heights of 8 feet).

  • In adults: acromegaly (overgrowth of hands, feet, and face).

• Hyposecretion of GH:

  • In children: pituitary dwarfism (may reach height of only 4 feet).

  • In adults: usually causes no problems.

Thyroid-Stimulating Hormone (TSH)

• A tropic hormone also called thyrotropin, produced by thyrotropic cells.

• Stimulates normal development and secretory activity of the thyroid gland.

• Release is triggered by thyrotropin-releasing hormone (TRH) from the hypothalamus.

• Inhibited by rising blood levels of thyroid hormones (negative feedback) and by GHIH.

Adrenocorticotropic Hormone (ACTH)

• Also called corticotropin, secreted by corticotropic cells.

• Precursor is pro-opiomelanocortin.

• Stimulates the adrenal cortex to release corticosteroids.

• Regulation:

  • Triggered by hypothalamic corticotropin-releasing hormone (CRH) in a daily rhythm (highest in the morning).

  • Release is influenced by internal/external factors such as fever, hypoglycemia, and stressors.

Gonadotropins (FSH and LH)

• Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are secreted by gonadotropic cells of the anterior pituitary.

• FSH stimulates production of gametes (egg or sperm).

• LH promotes production of gonadal hormones:

  • In females: helps mature follicles of egg, triggers ovulation, and release of estrogen and progesterone.

  • In males: stimulates production of testosterone.

• Absent from blood in prepubertal boys and girls.

• Regulation:

  • Triggered by gonadotropin-releasing hormone (GnRH) during and after puberty.

  • Suppressed by gonadal hormones (feedback inhibition).

Prolactin (PRL)

• Secreted by prolactin cells of the anterior pituitary.

• Role:

  • Stimulates milk production in females.

  • Role in males is not well understood.

• Regulation:

  • Primarily controlled by prolactin-inhibiting hormone (PIH), which is dopamine.

  • PIH prevents release of PRL until needed; decreased PIH leads to lactation.

  • Increased estrogen levels stimulate PRL (reason for breast swelling/tenderness during menstrual cycle).

  • Blood levels rise toward end of pregnancy; suckling stimulates PRL release and continued milk production.

Clinical Considerations: Prolactin Disorders

• Hypersecretion is more common than hyposecretion.

• Hyposecretion is only a problem in women who choose to nurse.

• Hyperprolactinemia (most frequent abnormality of anterior pituitary tumors):

  • Signs/symptoms: inappropriate lactation, lack of menses, infertility in females, impotence in males.

Table: Pituitary Hormones—Summary of Regulation and Effects

Hormone	Regulation of Release	Target Organs and Effects	Effects of Hyposecretion	Effects of Hypersecretion
Growth Hormone (GH)	Stimulated by GHRH; inhibited by GHIH (somatostatin)	Liver, muscle, bone, cartilage, other tissues; stimulates growth, mobilizes fats, spares glucose	Pituitary dwarfism in children	Gigantism in children; acromegaly in adults
Thyroid-Stimulating Hormone (TSH)	Stimulated by TRH; inhibited by feedback from thyroid hormones and GHIH	Thyroid gland; stimulates thyroid hormone release	Cretinism in children; myxedema in adults	Hyperthyroidism; effects similar to Graves' disease
Adrenocorticotropic Hormone (ACTH)	Stimulated by CRH; inhibited by feedback from glucocorticoids	Adrenal cortex; promotes release of glucocorticoids and androgens	Rare	Cushing's disease
Follicle-Stimulating Hormone (FSH)	Stimulated by GnRH; inhibited by feedback from sex hormones	Ovaries/testes; stimulates gamete production	Failure of sexual maturation	No significant effects
Luteinizing Hormone (LH)	Stimulated by GnRH; inhibited by feedback from sex hormones	Ovaries/testes; triggers ovulation, stimulates sex hormone production	Failure of sexual maturation	No significant effects
Prolactin (PRL)	Inhibited by PIH (dopamine); stimulated by decreased PIH, estrogens, suckling	Breast secretory tissue; promotes lactation	Poor milk production	Inappropriate milk production (galactorrhea); cessation of menses in females

Thyroid Gland

Anatomy and Histology

• Butterfly-shaped gland in the anterior neck, just inferior to the larynx.

• Consists of:

  • Isthmus: median mass connecting two lateral lobes.

  • Follicles: hollow spheres of epithelial follicular cells that produce glycoprotein thyroglobulin.

  • Colloid: fluid in follicle lumen containing thyroglobulin plus iodine; precursor to thyroid hormone.

  • Parafollicular cells: produce hormone calcitonin.

Thyroid Hormone (TH)

• The body's major metabolic hormone.

• Found in two forms:

  • T4 (thyroxine): major form, two tyrosine molecules with four bound iodine atoms.

  • T3 (triiodothyronine): two tyrosines with three bound iodine atoms; must be converted from T4 at tissue level.

• Both are iodine-containing amine hormones.

Effects of Thyroid Hormone

• Affects virtually every cell in the body.

• Enters target cell and binds to intracellular receptors within the nucleus, triggering transcription of metabolic genes.

• Major effects include:

  • Increases basal metabolic rate (BMR) and heat production (calorigenic effect).

  • Regulates tissue growth and development (critical for normal skeletal and nervous system development and reproductive capabilities).

  • Maintains blood pressure (increases adrenergic receptors in blood vessels).

Synthesis of Thyroid Hormone

1. Thyroglobulin is synthesized and discharged into follicle lumen.

2. Iodide ions (I-) are actively transported into the cell and released into the lumen.

3. Iodide is oxidized to iodine (I2).

4. Iodine is attached to tyrosine residues on thyroglobulin by peroxidase enzymes:

   • Monoiodotyrosine (MIT): one iodine attached.

   • Diiodotyrosine (DIT): two iodines attached.

5. MIT and DIT link to form T3 (one MIT + one DIT) or T4 (two DITs).

6. Colloid is endocytosed by follicular cells; vesicle combines with lysosome.

7. Lysosomal enzymes cleave T3 and T4 from thyroglobulin; hormones are secreted into the bloodstream.

Transport and Regulation

• T3 and T4 are transported by thyroxine-binding globulins (TBGs).

• T3 is 10 times more active than T4; peripheral tissues convert T4 to T3 by removing one iodine atom.

• TH release is regulated by negative feedback:

  • Falling TH levels stimulate TSH release.

  • Rising TH levels inhibit TSH (negative feedback).

  • TSH can also be inhibited by GHIH, dopamine, cortisol, and iodide.

  • TRH can override negative feedback during pregnancy or cold exposure.

Table: Major Effects of Thyroid Hormone (T3 and T4) in the Body

System	Normal Effects	Hyposecretion	Hypersecretion
BMR/Temperature	Promotes normal oxygen use and BMR; increases heat production	BMR below normal, decreased body temp, cold intolerance	BMR above normal, increased body temp, heat intolerance
Carbohydrate/Lipid/Protein Metabolism	Promotes glucose catabolism, mobilizes fats, essential for protein synthesis	Impaired glucose metabolism, elevated cholesterol	Enhanced catabolism, muscle wasting, weight loss
Nervous System	Promotes normal development and function	Infant: mental retardation; Adult: depression, sluggishness	Irritability, restlessness, insomnia
Cardiovascular	Promotes normal heart functioning	Decreased efficiency, low heart rate	Rapid heart rate, palpitations, high blood pressure
Muscular	Promotes normal muscle development and function	Sluggish muscle action, muscle cramps	Muscle atrophy, weakness
Gastrointestinal	Promotes normal GI motility and tone	Decreased motility, constipation	Increased motility, diarrhea
Reproductive	Promotes normal reproductive function	Impaired fertility, menstrual irregularities	Menstrual irregularities, impotence

Clinical Considerations: Thyroid Disorders

• Hyposecretion of TH in adults: myxedema

  • Symptoms: low metabolic rate, thick/dry skin, puffy eyes, feeling chilled, constipation, edema, mental sluggishness, lethargy.

  • If due to iodine deficiency: goiter (thyroid enlargement).

• Congenital hypothyroidism: usually due to poor development of thyroid gland; can cause developmental delays if untreated.

• Hypersecretion of TH: most common type is Graves' disease

  • Autoimmune disorder; antibodies mimic TSH, stimulating TH release.

  • Symptoms: elevated metabolic rate, sweating, rapid/irregular heartbeats, nervousness, weight loss, exophthalmos (protruding eyes).

  • Treatment: surgical removal of thyroid or radioactive iodine.

Calcitonin

• Produced by parafollicular (C) cells in response to high Ca2+ levels.

• Antagonist to parathyroid hormone (PTH).

• No known physiological role at normal levels, but at high doses:

  • Inhibits osteoclast activity and prevents release of Ca2+ from bone matrix.

  • Stimulates Ca2+ uptake and incorporation into bone matrix.

Parathyroid Gland

• Four to eight tiny yellow-brown glands embedded in the posterior aspect of the thyroid.

• Contain oxyphil cells (function unclear) and parathyroid cells that secrete parathyroid hormone (PTH).

• PTH is the most important hormone in Ca2+ homeostasis.

• Secreted in response to low blood Ca2+; inhibited by rising Ca2+ levels.

• Target organs: skeleton, kidneys, intestine.

Functions of PTH

• Stimulates osteoclasts to digest bone matrix and release Ca2+ to blood.

• Enhances reabsorption of Ca2+ and secretion of phosphate (PO43-) by kidneys.

• Promotes activation of vitamin D by kidneys, increasing absorption of Ca2+ by intestinal mucosa.

Clinical Considerations: Parathyroid Disorders

• Hyperparathyroidism (usually due to tumor):

  • Calcium leaches from bones, causing them to soften and deform.

  • Elevated Ca2+ depresses nervous system, contributes to kidney stones.

  • Osteitis fibrosa cystica: severe form with easily fractured bones.

• Hypoparathyroidism (following gland trauma/removal):

  • Can cause hypocalcemia, resulting in tetany, respiratory paralysis, and death.

Adrenal Gland

Anatomy and Structure

• Paired, pyramid-shaped organs atop the kidneys (suprarenal glands).

• Structurally and functionally two glands in one:

  • Adrenal cortex: three layers of glandular tissue that synthesize and secrete several different hormones.

  • Adrenal medulla: nervous tissue, part of the sympathetic nervous system.