Physiology Lectures 12-17

Hormone

Chemical signals secreted into the bloodstream that act on tissues

Endocrine

Hormone secreted into blood binds distant target cells

Paracrine

 Hormone acts locally by diffusing from its source to target cells in the neighborhood

Autocrine

Hormone acts on same cell that produced it

Steroids, protein/peptide hormones, amino acid analogues and derivatives

What are the three classes of hormones?

Ovaries, testes, adrenal cortex

Organs that secrete steroids

Mineralocorticoids, glucocorticoids, testosterone, estradiol

Examples of steroids

Anterior pituitary, thyroid, parathyroid, pancreas

Organs that secrete protein/peptide hormones

Insulin, prolactin, anti-diuretic hormone, oxytocin

Examples of protein/peptide hormones

Steroids

Which class of hormone originates from a cholesterol precursor?

Thyroid and adrenal medulla

Organs that secrete amino acid analogues and derivatives

Thyroxine, norepinephrine, and epinephrine

Examples of amino acid analogues and derivatives

External stimuli, internal stimuli, feedback loops

How are hormones regulated in the body?

Fright, cold, light cues

Examples of external stimuli

Blood sugar levels, hormonal signals from another gland

Examples of internal stimuli

Anterior

The hypothalamus synthesizes and releases regulating hormones that act on the ___ pituitary.

Posterior

The hypothalamus synthesizes hormones that are released from the ___ pituitary.

Oxytocin, antidiuretic hormone (ADH)

What hormones are synthesized by the hypothalamus and released from the posterior pituitary?

Releasing and inhibiting hormones

What hormones are synthesized and released from the hypothalamus to act on the anterior pituitary?

Peptide

What class do most hypothalamic releasing hormones belong to?

Dopamine

What is the only non-peptide hypothalamic releasing/inhibiting hormone?

Corticotropin releasing hormone (CRH)

1. Acts on corticotrophs in the anterior pituitary to stimulate production of ACTH

2. 41-amino acid protein is highly conserved (e.g., identical in humans and rats)

Gonadotropin releasing hormone (GnRH)

1. Acts on gonadotropes in the anterior-pituitary to stimulate production of follicle-stimulating hormone (FSH) and luteinizing hormone (LH)

   1. AKA luteinizing hormone releasing hormone (LHRH)

2. 10 amino acids

3. Very similar in different species

Growth hormone releasing hormone (GHRH)

1. Acts on somatotrophs in the anterior pituitary

2. Stimulates production of growth hormone (GH)

Growth hormone inhibiting hormone (GHIH)

1. AKA somatostatin

2. Acts on somatotrophs in the anterior pituitary

3. Inhibits production of GH

Thyrotropin releasing hormone (TRH)

1. TRH acts on thyrotrophs of the anterior pituitary to stimulate thyroid stimulating hormone (TSH)

2. 3-amino-acid peptide

Prolactin releasing hormone (PRH)

1. Acts on lactotrophs in the anterior pituitary

2. Stimulates production of prolactin (PRL)

Dopamine or prolactin inhibiting hormone (PIH)

1. Distinct ___-secreting neurons in hypothalamus

2. Enters portal vessels and is transported to the anterior pituitary

3. Acts on lactotrophs to inhibit production of prolactin by the anterior pituitary

Dopamine

What is the only non-peptide hormone?

Oxytocin

1. Stimulates smooth muscle contraction in the uterus and mammary glands

2. Uterine contraction and milk let-down

   1. Works with estrogen

   2. Inhibited by progesterone

   3. Short half-life

   4. Essential role in activating maternal behavior

   5. Role in social attachments and affiliations

   6. Positive interactions between humans and dogs linked with increase in oxytocin levels

   7. May increase trust among humans

Pitocin

Analogue of oxytocin

Used clinically to facilitate parturition and milk let-down

Has a short half-life and must be given repeatedly or continuously

Secreted at time of ejaculation; promotes contraction of ductus deferens (needed for contraction); may play a role in prostate function in dogs

Effects of oxytocin on males (even though role in males is unclear)

1. Suckling

2. Sight, sound, or smell of an infant

3. Dilation of the cervix

4. Orgasm

Stimulatory factors affecting oxytocin secretion

Opoids (endorphins)

Inhibitory factors affecting oxytocin secretion

Antidiuretic hormone (ADH) or Vasopressin

1. Acts on kidney tubules

   1. Decreases urine output

   2. Increases water resorption

2. Acts on sweat glands

   1. Decreases sweating

3. Acts on arterioles

   1. Constricts arterioles

   2. Increases blood pressure

4. Secreted in pulsatile fashion

Decreases, increases

ADH/Vasopressin acts on kidney tubules, which ___ urine output and ___ water resorption.

Decreases

ADH/Vasopressin acts on sweat glands, which ___ sweating.

Constricts, increases

ADH/Vasopressin acts on arterioles, which ___ arterioles and ___ blood pressure.

Fear, thirst, preanesthetic and anesthetic agents, the opioid methadone

Stimulating factors affecting ADH secretion

Satiation of thirst

Inhibitory factor affecting ADH secretion

V1

ADH receptor subtype on blood vessels

V2

ADH receptor subtype on renal collecting duct epithelial cells

V3

ADH receptor subtype on mediating ACTH secretion from the anterior pituitary

Hypertonic renal medulla

ADH facilitates diffusion of water from the collecting ducts into the ___.

V2

Which receptor subtype does ADH bind when facilitating diffusion of water into the hypertonic renal medulla

Adenylate cyclase, phosphorylation of proteins

What does ADH stimulate while facilitating diffusion of water into the hypotonic renal medulla

Aquaporins (AQP)

Permit water to pass from cell to interstitium

Diabetes insipidus

1. Abnormalities (lack) of ADH production or response

2. Little or no stimulation of ADH release due to sustained and excessive drinking

3. Significant disease in veterinary medicine

Central diabetes insipidus

Insufficient ADH release

Characterized by:

Dilute urine despite osmotic stimuli for ADH secretion

Absence of renal disease

Rise in urine osmolality following administration of ADH

Nephrogenic diabetes insipidus

Insufficient response of the kidney to ADH

Rarely congenital (more common in huskies than other dogs due to low affinity V2 receptor)

Acquired by down-regulation of AQP-2 due to tumors or endocrine disorder

Little/no response to desmopressin

Inter-cranial tumor in middle-aged and elderly animals, non-pituitary lesion, idiopathic form in young animals

Causes of central diabetes insipidus

Polyuria, polydipsia, near continuous demand for water, huge urine volume

Clinical manifestations of central diabetes insipidus

Diagnosis, treatment, and prognosis of central diabetes insipidus

Measure plasma ADH during osmotic provocation by hypertonic saline infusion

Treat with vasopressin (ADH) analogue (desmopressin)

In absence of tumor, long-term prognosis is good.

Treatment of nephrogenic diabetes insipidus

Treat with anti-diuretic drugs to increase water permeability in kidneys