Endocrine Physiology and Mechanisms of Hypothalamic-

Pituitary Regulation

Chapter 39

• Composed of cells and organs that are specialized to synthesize and secrete hormones into the bloodstream to act at distant target cells

• Hormones are blood-borne chemical messengers that affect target cells anatomically distant from the secreting cell

Endocrine System

How to go through the Endocrine System?

• What is the gland?• What triggers it to secrete?• What is the secreted product (hormone)?• What is the target of the hormone?• What is the resulting work of the hormone?

THEN…..

• Three things that make a gland secrete:

1. Hormonal stimulation– Hormone to hormone

• Hypothalamus pituitary• Pituitary thymus

2. Humoral fluids– What ions/proteins in the fluids

• Ca2+ levels, blood sugar

3. The Nervous System– Sympathetic stimuli

• Epinephrine and norepinephrine

Endocrine vs. Exocrine Glands

Where do they secrete their products?

Endocrine System

• Occurs when there is a drop in the level of a hormone– triggers a chain reaction of

responses to increase hormones in the blood

– most hormones are regulated by negative feedback

– OXYTOCIN: POSITIVE FEEDBACK

HORMONAL CONTROL

What is negative feedback?

Where is the hormone going?

• Only the target cells for a given hormone have receptors that bind and recognize that hormone.

Endocrine Glands

Endocrine GlandsEndocrine Glands

• Neurocrine—secretion of hormones into the bloodstream by neurons

• Endocrine—secretion of hormones into the bloodstream by endocrine glands

• Paracrine—hormone molecule secreted by one cell affects adjacent cells

• Autocrine—hormone molecule secreted by a cell affects the secreting cell

Hormones

• Water soluble– Peptides

– Tyrosine-derived catecholamines: • Epinephrine, Norepinephrine, Dopamine

• Lipid soluble– Tyrosine-derived Thyroid hormones:

• T3, T4

– Steroids

Hormones

Hormones: Tyrosine-derived catecholamines

Hormones: Tyrosine-derived thyroid hormones

Hormones: steroids

Hormones with Cell Membrane Receptors• Water-soluble hormones have a hormone-binding site located

on the external portion of a specific cell-surface receptor

• Hormones exert their action by binding to target cell receptor proteins

• Once binding takes place, a conformation of the receptor protein conveys a signal to the interior of the cell

• Amplification of the hormone activity is achieved by activation of a cascade of chemical reactions

Hormones: Mechanism of action

Hormones: Mechanism of actionHormones with Cell Membrane Receptors

Water Soluble Hormones

Hormones: Mechanism of actionHormones with Cell Membrane Receptors

Hormones with Intracellular Receptors• Lipid-soluble (thyroid and steroid) hormones diffuse easily through

the lipid bilayer of cell membranes

• Receptors for these hormones are located in the cytoplasm, or in the nucleus of the target cell

• Binding causes a change in affinity of the receptor for binding sites on DNA in the cell nucleus

• Gene expression is changed by binding of the hormone-receptor complex to specific DNA binding sites

• Onset of action of lipid-soluble hormones is slow compared with water-soluble hormones and there is no amplification cascade

Hormones: Mechanism of action

Lipid-Soluble Hormones

Hormone Synthesis, Secretion, Metabolism• Most endocrine hormones are polypeptides

manufactured on the rough endoplasmic reticulum and stored in vesicles within the cells

• Cleaved by specific enzymes to release the active form of the hormone

Hormones: Regulation

Pre hormone Hormone Cleavagefragment

Enzyme

Hormone Synthesis, Secretion, Metabolism• Water-soluble hormones

– Peptide hormones: CONTAINED WITHIN LIPID BILAYER OF THE VESICLES and stored until a trigger results in exocytosis of the hormone into the extracellular space

– Catecholamines: formed by enzymes within the cytoplasm that begin with tyrosine and through a series of steps convert it to dopamine, norepinephrine, or epinephrine

Hormones: Regulation

Hormone Synthesis, Secretion, Metabolism• Lipid-soluble hormones

– Steroid hormones: FORMED ON DEMAND from cholesterol that is stored in the cell or retrieved from the circulating lipoproteins

– Thyroid hormones: synthesis precedes secretion by weeks or months in the thyroid follicle and bound to protein thyroglobulin; secretion occurs via cleavage of the thyroid hormone based on systemic needs determined by the hypothalamus and pituitary gland

Hormones: Regulation

Pituitary Gland

Pituitary Gland

Pituitary Gland (Hypophysis)

• Located beneath the hypothalamus in the sella turcica

• Connected to hypothalamus by the pituitary stalk

• • Composed of anterior

(adenohypophysis) and posterior (neurohypophysis) lobes

Pituitary Gland

• Divided into two lobes– anterior pituitary lobe is larger and

produces SIX hormones; stimulated by releasing and inhibiting hormones from the hypothalamus; connected by hypophyseal portal veins

– posterior pituitary lobe is smaller and consists primarily of axons whose cell bodies are in the hypothalamus

HORMONES OF THE PITUITARY GLAND

Pituitary GlandPortal veins deliver releasing & inhibiting hormones from hypothalamus.

Sphenoid bone

Flow of Blood to Anterior Pituitary

• Releasing & inhibiting hormones enter blood (hypothalamus)• Travel through portal veins• Enter anterior pituitary at capillaries• Hormones travel to destination

Hypothalamic Neurosecretory Cells

•Does not synthesize hormones• Hormones packaged & travel by axons of hypothalamic neurons

Anterior vs. Posterior Lobes

•Growth Hormone (hGH)•Thyroid Stimulating hormone (TSH) •Follicle Stimulating Hormone (FSH)•Luteinizing hormone (LH)•Prolactin (PRL)•Adrenocorticotropic hormone (ACTH)

OxytocinAntidiuretic hormone

(ADH)

Anterior Pituitary Gland Hormones

• The hypothalamus regulates endocrine function of the ANTERIOR PITUITARY by SECRETING RELEASING AND INHIBITING HORMONES INTO THE PORTAL SYSTEM between the hypothalamus and pituitary that transports capillary blood from the hypothalamus to the capillaries of the anterior lobe

• Release of POSTERIOR PITUITARY hormones occurs WHEN ACTION POTENTIALS GENERATED IN THE HYPOTHALAMIC NEURONS TRAVEL DOWN THE AXONS of the pituitary stalk and trigger exocytosis of hormone from the nerve terminals in the posterior pituitary gland

Pituitary Gland

Pituitary Gland

Endocrine GlandsPosterior Pituitary Gland

Posterior Pituitary GlandTarget: V2 receptorsof distal renal tubule

cells

Aquaporins move from cytoplasm to

apical tubular epithelial cells

Water moves from tubular fluid

Cell

Interstitium

H20

What is diabetes insipidus?

-DECREASED ADH-Excretion of large amounts of dilute urine-Destruction of back of pituitary-OR insensitivity of kidneys to hormone

Endocrine GlandsAnterior Pituitary Gland

Hypothalamic neurons

Anterior Pituitary GlandHypothalamic hormones bind to receptors on pituitary cells

Thyroid Gland

Thyroid Gland

On each side of trachea is lobe of thyroid

Butterfly-shaped gland; located in the anterior part of neck

• Main function of thyroid is production and secretion of metabolically active hormones that are essential for regulation of

various metabolic processes.

• Thyroid hormones are made from tyrosine and iodine.

Thyroid Gland

– Secretes 3 hormones:• Thyroxine/ Tetraiodothyronine (T4)• Triiodthyronine (T3)• Calcitonin: Decreases the level of calcium

in the blood & increases uptake of calcium into bone matrix

THYROID

Thyroid Gland

Source: Clinical Chemistry. 2010. Kaplan and Pesce. Mosby.

Most important thyroid hormones are: - Thyroxin (T4) - Triiodothyronine (T3)

→ Approximately 90% of the thyroid hormone is in the form of T4, whereas 10% is T3

Thyroid•Follicle = sac of stored hormone

Makes thyroglobulin

Contains thyroglobulin with attached iodine molecules

Actions of Hormones from Thyroid Gland

• T3 & T4 : thyroid hormones responsible for our metabolic rate, synthesis of protein, breakdown of fats, use of glucose for ATP production

• Calcitonin: responsible for building of bone & stops reabsorption of bone by osteolasts (lowers blood levels of Calcium)

Thyroid Gland

Trap dietary iodine

Synthesize thyroglobulin + thyroid peroxidase

TSH stimulation

Control of T3 & T4 Secretion

• Negative feedback system• Low blood levels of

hormones stimulate hypothalamus

• It stimulates pituitary to release TSH

• TSH stimulates gland to raise blood levels

Parathyroid

• 4 pea-sized glands found on back of thyroid gland

• PTH: increases serum calcium and decreases serum phosphate

• PTH=Phosphate Trashing Hormone• 1. Increase bone reabsorption of calcium• 2. Increase kidney reabsorption of

calcium• 3. Decrease kidney reabsorption of

phosphate• 4. Increase Vitamin D production by

stimulating kidney (thus, indirect increase in intestinal calcium)

PARATHYROID GLANDS

Parathyroid hormone (PTH)

& Calcitonin (CT)

Adrenal Gland

• Two adrenal glands located on top of each kidney; each has two parts– Cortex

• Mineralocorticoids• Glucocorticoids• Androgens

– Medulla • epinephrine• norepinephrine

ADRENAL GLANDS

Regulation the three S’sSalt, sugar and sex

Adrenal Gland

Adrenal Glands

Adrenal Gland

Low blood flow

Adrenal Gland: Aldosterone

Glucocorticoid: Cortisol

• Glucose formation: gluconeogenesis (prime effect)• Breakdown of protein • (increase release of amino acids into blood stream)

• Breakdown of fat (lipolysis)• Depression of Immune function • (Prescribed for organ transplants)

• Anti-Inflammatory effects• (inhibit WBC’s but also retard tissue repair)

• Resistance to stress: Provide tissues with a ready supply of ATP

Adrenal Gland: Cortisol

Normally cortisol is present in the body at higher levels in the morning, and at its lowest at night.

Adrenal Gland: Cortisol

Categories of Endocrine Disease

• Hyposecretion• Hypersecretion• Target cell hyporesponsiveness

Categories of Endocrine Disease

• Hyposecretion – Primary hyposecretion occurs when an

ENDOCRINE GLAND releases an inadequate amount of hormone to meet physiologic needs

– Secondary hyposecretion occurs when secretion of a TROPIC HORMONE is inadequate to cause the target gland to secrete adequate amounts of hormone

Categories of Endocrine Disease (Cont.)

• Hypersecretion– Primary hypersecretion occurs when there is a

DYSFUNCTION OF THE ENDOCRINE GLAND that results in abnormally high secretion of hormone

– Secondary hypersecretion occurs when there is an ELEVATION IN THE TROPIC LEVEL of one hormone that results in an increased plasma concentration of the endocrine gland hormone also

Categories of Endocrine Disease

• Target cell hyporesponsiveness– Typically due to lack of or a deficiency in cellular

receptors, but can occur with postreceptor mechanisms, such as second-messenger dysfunction that causes decreased cellular response

– Hormone resistance of the target tissues will cause the same set of clinical symptoms as hyposecretion