Topic 3A: the endocrine system

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functions in regulation of specific targets to maintain homeostasis

made up of endocrine glands that secrete hormones

hormones: chemical messengers released from endocrine glands into the blood and travel to reach specific target cells/tissues/organs to regulate physiological processes; highly specific

exocrine glands: secretes its products onto a surface, into a body cavity, or within organs.

autocrine vs paracrine

endocrine glands: secrete hormones into the blood stream

the pancreas has both exo- (secretion of digestive enzymes into the small intestine) and endocrine (insulin and glucagon secretion) capabilities

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Types of Hormones:

lipid-derived/steroidal: tend to be cholesterol derivatives made from terpenoid precursors; receptors are intracellular; ex: estrogens, androgens, aldosterone, cortisol

mechanism of action:

binds to its cytoplasmic receptor by diffusing across the membrane

steroid-receptor complex moves into the nucleus and interacts with DNA

this results in a change in gene expression, such as production of a new protein which goes on to change cell function

amino-acid derived: generally water soluble, made of modified tyrosine or tryptophan; receptors are on the plasma membrane --> extracellular; ex: norepinephrine, epinephrine, thyroxine

peptide derived: polypeptide chains, extracellular receptors, ex: FSH, ADH, oxytocin, growth hormones

mechanism of action:

the hormone acts as a first messenger, never entering the cell as it is unable to cross the plasma membrane

binding to the receptor causes a cascade of events intracellularly (receptors are commonly GPCRs), ultimately producing a second messenger (if GPCR, then cAMP)

the second messenger then changes the function of the target cell by altering enzymatic activities and cellular reactions (cAMP activates protein kinases, setting off cascades)

prostaglandins: lipid-based molecules released by plasma membranes of cells, not secreted from endocrine glands. Function as local hormones with a variety of functions, such as regulation of body temperature, blood clotting, the inflammatory response, and menstrual cramping caused by uterine contractions.

hormones are specific to their receptors, as they encounter many molecules while traveling in the blood stream

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HPT axis: an interaction between the hypothalamus, (anterior) pituitary, and thyroid, which regulates metabolic rate, among other homeostasis functions

hypothalamus senses levels of T3 and T4, and secretes thyrotropin releasing hormone when they are low

TRH affects anterior pituitary, causing release of thyrotropin (TSH)

TSH causes release of T3 and T4 from thyroid

T3 and T4 have a negative feedback loop with thyroid and hypothalamus

HPA axis: significant interaction between hypothalamus, (anterior) pituitary, and adrenal (cortex) that effects multiple systems, but most significantly is involved in stress response

hypothalamus receives stress stimulus and secretes corticotropin releasing hormone

CRH affects anterior pituitary, which releases adrenocorticotropin hormone

ACTH affects adrenal cortex, which releases cortisol

cortisol has a negative feedback loop with both pituitary and hypothalamus

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Relationship with nervous system/Neuroendocrinology:

nervous system can override endocrine controls in certain situations

ex: situations of extreme stress or trauma

hormone feedback loops are controlled by the nervous system; neural stimuli trigger the release of hormones

blood hormone levels can impact neural activity (i.e. mood swings during menstruation)

dopamine is both a hormone and a neurotransmitter

the hypothalamus is the main link between the 2 systems; produces hormones that influence the pituitary gland, which then regulates other endocrine glands

Regulation of secretion:

negative feedback mechanism: response is opposite of the stimulus (if there are high levels of hormone, more hormone will not be secreted); tends to maintain homeostasis

ex: release of hormones to trigger the breakdown of bone tissue to release calcium in response to low blood calcium levels

ex: release of thyroid releasing hormone from the hypothalamus triggers release of TSH from anterior pituitary, stimulating release of thyroxine from thyroid. When blood [thyroxine] is sufficient, negative feedback mechanism stops the release from the hypothalamus

antagonistic relationships between hormones--> insulin and glucagon

positive feedback mechanisms: less common than negative; stimulus causes response that further amplifies the stimulus; tends to move away from homeostasis and generally short-lived

ex: pregnancy/childbirth hormones--> oxytocin secreted from the posterior pituitary promotes contractions during labor, as the baby moves through the cervix, pressure receptors signal the hypothalamus to produce more oxytocin

other mechanisms:

humoral stimuli: change in hormone secretion based on extracellular fluid changes

ex: change in blood [glucose] triggering the release of insulin or glucagon from the pancreas

hormonal stimuli: release of a hormone in response to another hormone

neural stimuli: nervous system triggers the release of hormones

ex: release of norepinephrine or epinephrine in response to stress signals from the sympathetic/parasympathetic systems

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hypothalamus: located in the brain, synthesizes ADH (antidiuretic hormone, aka vasopressin), oxytocin, GnRH, thyrotropin releasing hormone, corticotropin-releasing hormone, and growth hormone releasing hormone

oxytocin:

peptide hormone

positive feedback loop

secreted by posterior pituitary

function: contractions during labor and stimulation of milk secretion

vasopressin: aka ADH, antidiuretic hormone

peptide hormone

negative feedback loop

secreted by posterior pituitary

function: increases blood volume by keeping the kidneys from absorbing too much water and using vasoconstriction, increases blood pressure

thyrotropin-releasing hormone (TRH):

peptide hormone

negative feedback loop

function: regulates release of TSH from anterior pituitary

gonadotropin-releasing hormone (GnRH):

peptide hormone

function: regulates secretions of gonadotropins (FSH and LH) from anterior pituitary

positive feedback loop with estrogen

growth hormone releasing hormone (GhRH):

peptide hormone

function: regulates secretion of growth hormone (somatotropin) from anterior pituitary

negative feedback loop?

corticotropin-releasing hormone (CRH):

peptide hormone

function: regulates release of ACTH and cortisol in HPA axis

negative feedback loop

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Pituitary: aka the master gland, located at the base of the brain

anterior pituitary: produces FLAT PEG hormones

these hormones are known as tropic hormones because they affect the functioning of other organs; their production is regulated by the hypothalamus

the PEG hormones are direct hormones, because they act directly on non-endocrine organs

Follicle-stimulating hormone (FSH):

peptide hormone

both types of feedback

function: controls production of gametes in males and females, ovulation in women, sperm production in men

Lutenizing hormone (LH):

peptide hormone

both types of feedback

function: regulates sexual development in males and females

Adrenocorticotropic hormone (ACTH):

peptide hormone

negative feedback loop

function: regulates secretion of cortisol

Thyroid-stimulating hormone (TSH): aka thyrotropin

peptide hormone

negative feedback loop

function: regulates secretion of T3 and T4

Prolactin:

peptide hormone

function: regulates milk production (P for prolactin, P for production, NOT secretion)

Endorphins:

peptide hormone

function: released during stress, to reduce it and improve mood

Growth hormone (GH): aka somatotropin

peptide hormone

function: increased cell replication, bone development (osteoblasts at work), stimulation of the immune system, mobilization of glucose, increased protein synthesis, increased muscle mass

posterior pituitary: does not synthesize any hormones, however secretes ADH and oxytocin

posterior pituitary hormones are the exception, because they are synthesized in the hypothalamus and secreted by the pituitary

ADH/Vasopressin

Oxytocin

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thyroid: located in the neck, produces T3 (triiodothyronine) and T4 (thyroxine), and calcitonin

T3: triiodothyronine

amino acid derived hormone

negative feedback loop

function: increases basal metabolic rate

T4: thyroxine

amino acid derived hormone

negative feedback loop

function: increases basal metabolic rate

Calcitonin:

peptide hormone

negative feedback loop

function: decreases blood calcium level by activating osteoclasts

parathyroid glands: located on the posterior of the thyroid; most people have 4, however range from 2-6, produce parathyroid hormone --->

peptide hormone

negative feedback loop

function: increases blood calcium levels and regulates phosphorous levels

pineal gland: in the center of the brain between the 2 hemispheres, produces melatonin

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adrenal glands:

pair (medulla and cortex) of ductless glands located above the kidneys

adrenal medulla:

produces epinephrine and norepinephrine---->

amino acid derived hormones

catecholamines

function: activate sympathetic nervous system

adrenal cortex:

aldosterone:

steroid hormone

function: increases blood volume by increasing sodium absorption and potassium release at kidney, thereby increasing BP

negative feedback loop

cortisol:

steroid hormone

function: curbs non-essential functions and enhances survival mechanism (like mobilization of glucose)

negative feedback loop

androgens and estrogens:

steroid hormones

function: development of secondary sexual characteristics

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pancreas: located between the stomach and small intestine, contains both exocrine and endocrine cells

glucagon:

peptide hormone

produced by alpha cells of islets of Langerhans

negative feedback loop/antagonist to insulin

function: increases blood sugar level by promoting gluconeogenesis, glycogenolysis, etc.

insulin:

peptide hormone

produced by beta cells of islets of Langerhans

negative feedback loop/antagonist to glucagon

function: decreases blood sugar level by promoting glycogenesis, glucose uptake by cells, etc.

somatostatin:

peptide hormone

produced by delta cells of islets of Langerhans

function: inhibits release of glucagon and insulin and growth hormone

amylin:

co-secreted by beta cells with insulin, synergist

gonads: the primary reproductive organs including male testes and female ovaries

ovaries:

progesterone:

steroid hormone

both positive and negative feedback mechanisms

function: prepares endometrium for potential fetal implantation after ovulation

estrogen:

steroid hormone

exerts both positive and negative feedback mechanisms

function: development of reproductive system, other effects on other organ systems