Bio 1.5 Endocrine system

endocrine signalling

involves the secretion of hormones directly into the bloodstream. The hormones travel to distant target tissues, where they bind to receptors and induce a change in gene expression or cell function. 

Peptide hormones

are composed of amino acids and are derived from larger precursor proteins that are cleaved during posttranslational modification. 

Peptide hormones are polar and cannot pass through the plasma membrane. 

These hormones bind to extracellular receptors, where they trigger the transmission of a second messenger. 

eg cAMP, IP3 and calcium

Each step of the signaling cascade can induce amplification of the signal. [each stope can result in increase intensity]

Peptide hormones exert effects that usually have rapid onset but are short lived. 

These hormones are water-soluble, so they travel freely in the bloodstream and do not require a special carrier. 

smaller units are transported to golgi apparatus for further modifications that activate the hormone, released via exocytosis

GPCR

when a peptide hormones binds to a GPCR it triggers the receptor to activate or inhibit adenylate cyclase > raising or lowering the levels of cAMP accordingly.

cAMP can bind to intracellular targets such as protein kinase A which phosphorylates transcription factors like cAMP response to exert the hormone’s ultimate effect

steroid hormones

derived from cholesterol.
Steroid hormones are minimally polar and can pass through the plasma membrane. hence their receptors are intracellular (in they cytosol) or intranuclear (in the nucleus)

These hormones bind to and promote a conformational change in cytosolic or intranuclear receptors; the hormone–receptor complex binds to DNA, altering the transcription of a particular gene. 

eg dimerization (pairing of 2 receptor hormone complexes)

Steroid hormones exert effects that usually have slow onset but are long- lived. 

Because these hormones are lipid-soluble, they cannot dissolve in the bloodstream and must be carried by specific proteins. 

hormones are generally inactive while attached to a carrier protein and must dissociate from the carrier to function.

AA derivative hormones

are modified amino acids. 

Their chemistry shares some features with peptide hormones and some features with steroid hormones; different amino acid–derivative hormones share different features with these other hormone classes. 

Common examples are epinephrine, norepinephrine [bind to GPCRs], triiodothyronine, and thyroxine.[bind intracellularly] 

Hormones can be classified by their target tissues.

direct vs tropic hormones

direct hormones

 have major effects on non-endocrine tissues

act directly on target tissue

tropic hormones

have major effects on other endocrine tissues. 

require an intermediary to act

usually originate in the brain

most steroid hormones

–one, –ol, or –oid

most peptide hormones

–in or –ine

hypothalamus

is the bridge between the nervous and endocrine systems. 

The release of hormones from the hypothalamus is mediated by a number of factors, including projections from other parts of the brain, chemo- and baroreceptors in the blood vessels, and negative feedback from other hormones. 

hypothalamus controls the pituitary through paracrine release of hormones into a portal system that directly connects the 2 organs.

negative feedback

 final hormone (or product) of a pathway inhibits hormones (or enzymes) earlier in the pathway, maintaining homeostasis. 

anterior pituitary

The hypothalamus stimulates the anterior pituitary gland through paracrine release of hormones into the hypophyseal portal system, which directly connects the two organs. 

hypothalamic–pituitary–adrenal (HPA) axis

a crucial neuroendocrine system that regulates the body's stress response, involving the hypothalamus, pituitary gland, and adrenal glands, and plays a vital role in maintaining homeostasis and responding to stress.

hypothalamic–pituitary–ovarian (HPO) axis

a complex system that regulates the female reproductive cycle, involving the hypothalamus, pituitary gland, and ovaries, with hormones like GnRH, FSH, LH, estrogen, and progesterone playing key roles. 

Gonadotropin-releasing hormone (GnRH)

promotes the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). 

Growth hormone–releasing hormone (GHRH)

promotes the release of growth hormone. 

[AP] Thyroid-releasing hormone (TRH)

promotes the release of thyroid- stimulating hormone (TSH). 

Corticotropin-releasing factor (CRF)

promotes the release of adrenocorticotropic hormone (ACTH). 

Prolactin-inhibiting factor (PIF or dopamine)

inhibits the release of prolactin. 

posterior pituitary

interactions with the posterior pituitary occur via the axons of nerves projected by the hypothalamus directly. 

eg Antidiuretic hormone (ADH or vasopressin) and oxytocin are synthesized in the hypothalamus and then travel down these axons to the posterior pituitary, where they are released into the bloodstream. 

[AP] FSH

promotes the development of ovarian follicles in females and spermatogenesis in males. 

[AP] LH

promotes ovulation in females and testosterone production in males. 

[AP] ACTH

promotes the synthesis and release of glucocorticoids from the adrenal cortex. 

[AP] TSH

promotes the synthesis and release of triiodothyronine and thyroxine from the thyroid. 

[AP] prolactin

promotes milk production.

Prolactin is an unusual hormone in that the release of dopamine from the hypothalamus decreases its secretion

[AP] endorphins

decrease perception of pain and can produce euphoria. 

[AP] Growth hormone (GH)

promotes growth of bone and muscle and shunts glucose to these tissues. It raises blood glucose concentrations

is energetically expensive and requires large quantities of glucose. Growth hormone prevents glucose uptake in certain tissues (those that are not growing) and stimulates the breakdown of fatty acids. This increases the availability of glucose overall, allowing muscle and bone to use it. GH release is stimulated by growth hormone–releasing hormone (GHRH) from the hypothalamus.

An excess of GH released in childhood (before this closure) can cause gigantism, and a deficit results in dwarfism. In adults, the situation is slightly different. Because the long bones are sealed, GH still has an effect, but it is primarily in the smaller bones.

[Posterior] ADH

is secreted in response to low blood volume (as sensed by baroreceptors) or increased blood osmolarity (as sensed by osmoreceptors) and increases reabsorption of water in the collecting duct of the nephron, increasing blood volume and decreasing blood osmolarity. 

[Posterior] Oxytocin

is secreted during childbirth and promotes uterine contractions. It also promotes milk ejection and may be involved in bonding behavior. It is unusual in that it has a positive feedback loop, not negative. 

thyroid

 is located at the base of the neck in front of the trachea; it produces three key hormones. 

1. T3

2. T4

3. calcitonin

setting basal metabolic rate and promoting calcium homeostasis

[thyroid] T3 (Triiodothyronine) , T4 (thyroxine)

are produced by follicular cells and contain iodine. (iodinationation of the amino acid tyrosine in the follicular cells of the thyroid)

They increase basal metabolic rate and alter the utilization of glucose and fatty acids.

increased T3 and T4 lead to increasse cellular respiration.

Thyroid hormones are required for proper neurological and physical development in children. 

hypothyroidism

deficiency of iodine or inflammation of the thyroid

thyroid hormones are secreted in insufficient amounts or not at all. The condition is characterized by lethargy, decreased body temperature, slowed respiratory and heart rate, cold intolerance, and weight gain.

hyperthyroidism

which may result from a tumor or thyroid overstimulation

heightened activity level, increased body temperature, increased respiratory and heart rate, heat intolerance, and weight loss.

[thyroid] calcitonin

is produced by parafollicular (C) cells. It decreases plasma calcium concentration by promoting calcium excretion in the kidneys, decreasing calcium absorption in the gut, and promoting calcium storage in bone. 

Calcitonin tones down calcium levels in the blood.

[parathyroid glands] PTH

The parathyroid glands release parathyroid hormone (PTH), which increases blood calcium concentration. 

PTH decreases excretion of calcium by the kidneys and increases bone resorption directly to increase blood calcium concentration. 

PTH activates vitamin D, which is necessary for calcium and phosphate absorption from the gut. 

PTH promotes resorption of phosphate from bone and reduces reabsorption of phosphate in the kidney, but vitamin D promotes absorption of phosphate from the gut; these two effects on phosphate concentration somewhat cancel each other out. 

PTH is also subject to feedback inhibition.

calcium

is an exceptionally important ion. The critically important functions of calcium include:

• Bone structure and strength

• Release of neurotransmitters from neurons

• Regulation of muscle contraction

• Clotting of blood (calcium is a cofactor)

• plays a role in cell movement and exocytosis of cellular materials.

adrenal cortex

located on top of the kidneys. Each adrenal gland consists of a cortex and a medulla

produces three classes of steroid hormones.

1. Glucocorticoids 

2. Mineralocorticoids

3. Cortical sex hormones

[adrenal cortex] Glucocorticoids

regulate glucose levels and affect protein metabolism

such as cortisol and cortisone increase blood glucose concentration (by increasing gluconeogensis), reduce protein synthesis, inhibit the immune system, and participate in the stress response.

Glucocorticoid release is stimulated by ACTH. 

[adrenal cortex] mineralocorticoids

such as aldosterone promote sodium reabsorption in the distal convoluted tubule and collecting duct, thus increasing water reabsorption. Aldosterone also increases potassium and hydrogen ion excretion. Aldosterone activity is regulated by the renin–angiotensin– aldosterone system, not ACTH. 

RAAS

Decreased

blood pressure causes the juxtaglomerular cells of the kidney to secrete renin,

which cleaves an inactive plasma protein, angiotensinogen, to its active form,

angiotensin I. Angiotensin I is then converted to angiotensin II by angiotensin-

converting enzyme (ACE) in the lungs. Angiotensin II stimulates the adrenal

cortex to secrete aldosterone. Once blood pressure is restored, there is a decreased drive to stimulate renin release, thus serving as the negative feedback

mechanism for this system.

[adrenal cortex] cortical sex hormone

include androgens (like testosterone) and estrogens in both males and females. 

adrenal medulla

is derived from the nervous system and secretes catecholamines into the bloodstream. 

 production of the sympathetic hormones epinephrine and norepinephrine

[adrenal medulla] catecholamines

include epinephrine and norepinephrine, which are involved in the fight-or-flight (sympathetic) response. 

These hormones promote glycogenolysis, increase the basal metabolic rate, increase heart rate, dilate the bronchi, and alter blood flow. 

pancreas

 produces hormones that regulate glucose homeostasis. 

1. α-cells 

2.  β-cells 

3. δ-cells

[pancreas] alpha cells

Glucagon is produced by α-cells and raises blood glucose levels by stimulating protein and fat degradation, glycogenolysis, and gluconeogenesis. 

Glucagon levels are high when glucose is gone.

[pancreas] beta cells

insulin is produced by β-cells and lowers blood glucose levels by stimulating glucose uptake by cells and promoting anabolic processes, like glycogen, fat, and protein synthesis.

hypoglycemia

characterized by low blood glucose concentration

diabetes mellitus

excess glucose in the blood

type 1 and type 2

diabetes mellitus type 1

Type I (insulin-dependent) diabetes

mellitus is caused by autoimmune destruction of the β-cells of the pancreas,

resulting in low or absent insulin production. People who have type I diabetes

require regular injections of insulin to prevent hyperglycemia and to permit

uptake of glucose into cells.

diabetes mellitus type 2

(non-insulin-dependent) diabetes mellitus is

the result of receptor-level resistance to the effects of insulin. Type II diabetes

mellitus is partially inherited and partially due to environmental factors, such as

high-carbohydrate diets and obesity.

polyuria

increased frequency of urination

polydipsia

increased thirst

[pancreas] S cells

Somatostatin is produced by δ-cells and inhibits insulin and glucagon secretion. 

High blood glucose and amino acid concentrations stimulate its secretion.

gonads

produce hormones that are involved in the development and maintenance of the reproductive systems and secondary sex characteristics. 

eg testes, ovaries

[gonads] testes

secrete testosterone promotes the development and maintenance of secondary sex characteristics in males

[gonads] ovaries

secrete estrogen and progesterone development of the female reproductive system during gestation and also promotes the development and maintenance of secondary sex characteristics in females

pineal gland

releases melatonin, which helps to regulate circadian rhythms. 

kidneys

 secrete erythropoietin, which stimulates bone marrow to produce erythrocytes (red blood cells) in response to low oxygen levels in the blood. 

atria of the heart 

secrete atrial natriuretic peptide (ANP), which promotes excretion of salt and water in the kidneys in response to stretching of the atria (high blood volume). 

thymus

secretes thymosin, which is important for proper T-cell development and differentiation.