Endocrinology

I. Introduction

A. History

B. Definitions
1. Endocrine
-blood-borne chemical secreted by one cell and acting on another target cell
2. Paracrine
-chemical secreted by one cell acting on neighboring cell (local effect)
3. Autocrine
-chemical secreted by one cell acts on itself

C. Categories of hormones
1. Protein/peptide hormones
a. composed of amino acids
b. soluble in water
c. Examples:
-all hypothalamic hormones
-all pituitary hormones
-insulin
d. mechanism
-binds to cell surface receptor
-activates second messenger system
Examples:
-modification of pre-existing protein (e.g. second messenger system results in phosphorylation of target protein)
-regulation of ion channels
e. storage in secretory granules in cells

2. Steroids
a. synthesized from common precursor-cholesterol
- made up of 4 rings
- various different steroids are synthesized in each tissue depending on what steroidogenic enzymes are present
b. Examples:
-aldosterone
-sex steroids
-cortisol
c. Solubility-liphophilic, so poorly soluble in plasma
-transported in blood bound to binding protein such as androgen binding protein
d. Mechanism
-binding to intracellular receptor
-binding of hormone-receptor complex directly on target DNA
-regulation of transcription of specific target genes
-can induce production of specific proteins
e. not stored in cells but diffuse freely across cell membranes

3. Amines
a. synthesized from a single amino acid
b. types of amines
-thyroid hormones (T3 and T4)
-catecholamines (epinephrine, norepinephrine and dopamine)
c. solubility
catecholamines-hydrophilic
thyroid hormones-lipophilic
d. mechanism of action
-catecholamines act through the same mechanism as protein hormones
-thyroid hormones act via the same mechanism as steroid hormones
e. thyroid hormones circulate bound to thyroid binding proteins

D. Factors affecting hormone concentrations
1. Rate of production or secretion
a. may be affected by other trophic or inhibitory hormones
-e.g. TSH (the anterior pituitary hormone thyroid stimulating hormone) causes release of thyroid hormones and TRH (thyrotropin releasing hormone) is a hypothalamic hormone which causes release of TSH from the anterior pituitary
b. neuroendocrine reflexes
-stimulation of the nervous sytem affects hormone production or release
-examples: stimulation of the cervix in cats and rabbits causes release of LH and subsequent ovulation or milk ejection reflex
c. circadian and circannual rhythms
-temporal patterns of hormone release
e.g. nocturnal rise in ADH
e.g. pituitary hormones in seasonal breeding animals
2. Metabolism and excretion
-liver metabolism
-metabolism by gut microbes
-elimination in feces and urine
etc
3. Binding protein concentrations
-generally only free hormone is active

E. Factors affecting hormone action
1. Number of receptors and strength of binding
2. Presence of other hormones
-e.g. antagonists
3. Second messenger systems

F. Endocrine Disorders
1. Hypersecretion
a. primary
-problem with gland itself causes oversecretion
e.g. tumor which produces the hormone
b. secondary
-overproduction of trophic hormone causes target gland to overproduce the hormone in question

2. Hyposecretion
a. primary
-genetic defect (e.g. lack of or mutated steroidogenic enzyme)
-dietary deficiency (e.g. lack of iodine which is necessary for synthesis of thyroid hormones)
-destruction of gland by disease or injury (e.g. autoimmune destruction of pancreatic Beta cells which produce insulin)
b. secondary
-underproduction of trophic hormone

3. Abnormal target cell responsiveness e.g. insulin resistance
a. defect in hormone receptors
b. disorder of second messenger system

4. Altered metabolism of hormone
-example is effect of antibiotics on oral contraceptives

II. Hypothalamic-Pituitary Axis

A. Hypothalamus
-portion of the CNS located between the optic chiasm and near the third ventricle

B. Pituitary gland
1. Located at base of skull
2. Connected to the hypothalamus by the hypothalamic-pituitary stalk
3. Two portions of the pituitary:
a. posterior pituitary (aka neurohypophysis)
-neural tissue containing axons of nuclei located in the hypothalamus. Thus, posterior pituitary hormones are synthesized in the hypothalamus and are secreted in the posterior pituitary.
b. anterior pituitary (aka adenohypophysis)
-glandular tissue
-receives hypothalamic input via hormones secreted by the hypothalamus into hypophyseal portal blood vessels

C. Posterior Pituitary Hormones
1. ADH/vasopressin
2. Oxytocin

D. Anterior Pituitary Hormones
1. FSH (follicle stimulating hormone)
2. LH (luteinizing hormone)
3. TSH (thyroid stimulating hormone)
4. Growth hormone
5. Adrenocorticotrophic hormone (ACTH)
6. Prolactin

E. Hypothalamic hormones
1. Releasing hormones (are released into portal blood and cause release of specific anterior pituitary hormones)
-TRH (thyrotropin releasing hormone)
-CRH (corticotropin releasing hormone)
-GnRH (gonadotropin releasing hormone)
-GHRH (growth hormone releasing hormone)
-Somatostatin (growth hormone inhibiting hormone)
-PRH (prolactin releasing hormone)
2. Prolactin inhibiting hormone (dopamine)

III. Feedback Systems

A. Feedback systems are the primary means by which the endocrine system maintains a relatively constant rate of secretion
1. homeostasis is the general rule for the endocrine system, except for “special” events such as growth and reproduction, where the body wants to do something different rather than maintaining the status quo.

B. Types of feedback
1. Negative feedback
-control mechanism by end-products
-exists when the output of the system opposes a change in input
-important homeostatic mechanism
Example: testosterone feeds back on LH to inhibit LH release
2. Positive feedback
-occurs when homeostasis is not the goal (e.g. positive feedback of estradiol on release of LH to induce ovulation)
-the output of the system stimulates the input, which then stimulates more output, which stimulates more input, etc.