Chapter 11 Endocrine System

The Endocrine System

• Hormones are regulatory molecules secreted into the blood by endocrine glands.

Hormones

• Are secreted into the bloodstream by endocrine glands. The blood carries them to specific target cells that contain specific receptors for the hormones which causes a response from those target tissues.

• Some specialized neurons particularly in the hypothalamus secrete  chemical messengers into the blood rather into  a synaptic cleft,

• In addition, a number of chemicals such as, epinephrine and adrenaline are secret as both neurotransmitter and a omr

Hormone/Neurotransmitter commonalities

1. Target cells must possess specific receptors for that molecule

2. Binding of regulatory molecules to its receptor must cause a change in the target cell's activity.

3. A mechanism must in place to turn turn off the action of regulator or physiological control would be impossible

Hormone Interactions

• Hormone interactions can either be 1) synergistic or 2) antagonistic 

Mechanism of Hormone Action

• The chemistry of a hormone is mechanism of action, in other words how it does its job

• Polar hormones do not enter their target cells but instead bind to receptors on the plasma membrane. These hormones exert their effects through second messenger systems.

• Nonpolar hormones can pass through the plasma membrane and so bind to receptor proteins within their target cell. These are nuclear receptors which regulate gene expression.

Mechanisms of Steroid Hormone Action

• Steroid hormones are transported in the blood by carrier proteins

• The hormone separates from the carrier and passes through the plasma membrane

• Hormone travels into the nucleus and binds to DNA within the promoter region acting as a transcription factor.

• This stimulates genetic transcription and protein formation

• The production of new protein produces the hormonal effect.

Receptors for Steroid Hormones

• Each Steroid hormone receptors protein has a ligand-binding domain and a DNA binding domain which binds to the hormone response element of DNA near the promoter region. Binding to the hormone causes the receptor to attach on the half sites of the response elements. This promotes genetic transcription of the gene.

Thyroid Hormones

• The major hormone secreted by the thyroid gland is thyroxine. The thyroid also produces a small amount of triiodothyronine or T3. Once T4 enters target cells it is immediately converted to T3. Thyroid hormones regulate metabolism in the adult and nervous system development in the embryo/fetus.

Thyroid Hormone Mechanism of Action (free response)

• Thyroxine (T4) is carried in the bloodstream by a carrier protein

• The hormone disassociates from the carrier and passes through the plasma membrane 

• T4 is converted to T3 by removal of an iodine atom. 

• T3 binds to an intracellular carrier protein to be shuttled into the nucleus and once again dissociates. 

• Within the nucleus T3 binds a receptor protein which acts as a transcription factor stimulating the production of mRNA and subsequent protein synthesis.

Adenylate Cyclase as a second Messenger system

• A hormone such as epinephrine binds to its receptor in the plasma membrane

• The alpha subunit travels through the membrane to activate the enzyme  adenylate cyclase

• Adenylate cyclase converts ATP to cyclic AMP (cAMP)

• cAMP then removes an inhibiting regulatory subunit from a protein kinase in turn activating it.

• Activated protein kinases can then activate or deactivate other intracellular enzymes through phosphorylation

The Phospholipase C-Ca^2+ Second Messenger System

• A hormone binds to its receptor in the plasma membrane of its target cell

• G-proteins disassociate

• Phospholipase C is activated converting a particular membrane phospholipid into its breakdown products diacylglycerol (DAG) and IP3 (inositol triphosphate)

• IP3 enters into the cytoplasm and binds to calcium channel receptors on the endoplasmic reticulum.

• Sequestered Ca2+ diffuses out and intracellular Ca2+ concentrations rise.

• Ca2+ can then act as a second messenger itself activating protein kinases.

Adrenalin (Epinephrine) Works Two Ways

• Epinephrine uses two second messenger systems to exert its effects as shown in the illustrated liver cell. First binding to one type of receptor leads to cAMP production and activated protein kinases.

• Simultaneously binding to a second type of receptor on the same cell activates the phospholipase C-Ca2+ second messenger system leading to the activation of other protein kinases in the cascade of events that eventually converts glycogen to free glucose.

The Anterior Pituitary

1. Adrenocorticotropic Hormone (ACTH)

2. Thyroid-stimulating hormone (TSH)

3. Growth Hormone (GH)

4. Follicle Stimulating hormone (FSH)

5. Prolactin (PRL)

6. Luteinizing hormone (LH)

Pituitary Gland Adrenocorticotropic hormone (ACTH)

• Adrenocorticotropic hormone targets cells of the adrenal cortex stimulating the secretion of glucocorticoids such as cortisol which is involved in the stress response 

Thyroid Stimulating Hormone

• Targets cells in the thyroid gland stimulating their secretion of the thyroid hormones such as T3 and T4. These hormones are involved in regulating metabolism and development maintenance of the nervous system.

Growth Hormone

• Growth hormone targets most body tissues and promotes protein synthesis and growth.

• Growth Hormone stimulates growth of 

1. Muscle

2. bone

Follicle Stimulating Hormone

• Targets gonadal tissues to promote gamete production and stimulates estrogen production from the ovary 

• Gametes

- Eggs in ovary

- Sperm cells in testis

Prolactin 

• Targets the mammary glands that produce milk. Prolactin Stimulates lactation which is milk production in the postpartum female. Remember difference between prolactin and oxytocin which are both required to nurse and infant

Luteinizing Hormone (LH)

• Luteinizing hormone (LH) targets the gonads to stimulate sex hormone secretion

• Stimulates ovulation and corpus luteum formation after ovulation in females

• Testosterones secretion from interstitial cells in males.

Anterior Pituitary Hormones

• Adrenal Cortex- stimulates secretion of glucocorticoids

• Thyroid gland - stimulates secretion of thyroid hormones

• Most Tissue - promotes protein synthesis and growth; lipolysis and increased blood glucose

• Gonads - Promotes gamete production and stimulates estrogen production in females

• Mammary glands and other sex accessory organs- promotes milk production in lactating females; additional actions in other organs

• Gonads - stimulates sex hormone secretion; ovulation and corpus luteum formation in females; stimulates testosterone secretion in males.

Posterior Pituitary 

• Stores and releases two hormones, both of which are produced in the hypothalamus

1. Antidiuretic hormone (ADH) - Stimulates water retention by the kidneys, so that less water is excreted in the urine

2. Oxytocin stimulates contractions of the uterus during birth. Also stimulates contractions of the mammary glands and ducts resulting in milk ejection during suckling

Hypothalamic Control of Posterior Pituitary Oxytocin

• Oxytocin release is caused by the baby suckling at the nipple. This sensory input projects to the oxytocin secreting cells in the thalamus. These cells then fire an action potential to their axon terminals in the posterior pituitary where oxytocin is secreted into the bloodstream.

Hypothalamic control of Posterior Posterior Pituitary ADH

• ADH is stimulated by osmoreceptor neurons in the hypothalamus in response to a rise in osmolality. An increased osmolality shrinks these cells which results in actions potentials projected down these axons to the posterior pituitary gland

• ADH is inhibited by stretch receptors in the heart, which are stimulated when there is a rise in blood volume.

Hypothalamic Control of the Anterior Pituitary

• Because axons do not enter the anterior pituitary, hypothalamic control of the anterior pituitary is achieved through chemical rather than neural regulation. Releasing and inhibiting hormones produced by neurons in the hypothalamus are carried to the anterior pituitary where they exert their effects.

Feedback Inhibition of Thyroid Hormone

• The secretion of thyroxine from the thyroid begins with the secretion of thyrotropin releasing hormone( TRH ) from the hypothalamus which leads to secretion of the thyroid stimulating hormone (TSH) from the anterior pituitary. Which binds to receptors on cells of the thyroid gland to secrete thyroid hormone. 

Feedback inhibition of Thyroid hormone Exam question

• Negative feedback inhibition acts on this system in two ways. Elevated thyroxine levels in the blood 1) inhibits the pituitary’s response to thyrotropin-releasing hormone and 2) inhibits the secretion of thyrotropin-releasing hormone from the hypothalamus in the first place. Both mechanisms combined lead to decreased circulating thyroxine levels.

Feedback Inhibition of Sex Steroids

• Negative feedback of the sex steroids estrogen and testosterone acts in a similar manner. Increasing levels of the sex steroids in the blood 1) inhibits the pituitary’s response to gonadotropin-releasing hormone (GnRH) from the hypothalamus and 2) inhibits the secretion of GnRH from the hypothalamus in the first place. Both mechanisms combine leading to decreased circulating levels of the sex steroids. 

Adrenal Glands 

• The adrenal gland is composed of an outer adrenal cortex and inner adrenal medulla. The adrenal medulla secretes epinephrine and norepinephrine and is under the control of the sympathetic division of the autonomic nervous system. The adrenal cortex secretes steroid hormones that participate in the regulation of mineral and energy balance and also secretes  which is a hormonal response to stress.

The Pituitary-Adrenal Axis and Cortisol

• Stress perceived by higher brain centers leads to the secretion of corticotropin-releasing hormone (CRH) from the hypothalamus. Increased releasing hormone leads to increased secretion of adrenocorticotropic hormone (ACTH) from the anterior pituitary gland and secretion of the stress hormone cortisol from the adrenal gland into the bloodstream

• Cortisol levels can increase in the blood up to six times normal levels and in the short term leads to increased blood glucose levels and metabolism and reduced inflammation. However, long term amplifications of cortisol effects are deleterious effects including effects on memory, anxiety, depression and can lead to insulin resistant diabetes. Prolonged stress can literally kill you.

Thyroid Gland

• As previously stated the thyroid gland produces thyroxine (T4) and triiodothyronine (T3) which are needed for proper growth and development and which are primarily responsible for determining the basal metabolic rate. The thyroid gland is located just below the larynx and is composed of two lobes.

• The  parathyroid glands are located on the posterior aspect of the thyroid gland 

How Iodine Deficiency causes a Goiter

• Thyroid stimulating hormone stimulates the thyroid to secrete thyroxine. However, it also exerts a growth effect on the thyroid gland itself. A lack of iodine causes hypothyroidism, and the resulting elevation in thyroid stimulating hormone stimulates excessive growth of the thyroid gland resulting in the development of a goiter. 

• Iodine Is needed to make the thyroid hormones (T3 and T4). Lack of adequate hormone production ( because of lack of iodine) decreases the inhibition of TRH and TSH. Excess thyroid stimulating hormone (TSH) grows the thyroid gland in the absence of normal thyroid hormone production.

Cretinism 

• is a condition of severely stunted physical and mental growth due to untreated congenital deficiency of thyroid hormones. Can be caused by lack of iodine in the mother, lack of development of a thyroid gland, or lack of thyroxine receptors in brain

Grave’s Disease

• Exhibits bulging eyes due to overstimulation of the thyroid gland by an autoimmune response that activates the thyroid stimulating hormone receptors.

• People with Graves disease are hyperthyroid. They are sensitive to heat, suffer heart palpitations and have other metabolic problems

Parathyroid Gland

• The parathyroid glands are embedded in the posterior surface of the thyroid gland and there are usually 4 of them. They are very small. They secrete only 1 hormone, parathyroid hormone which promotes an increase in blood calcium levels by acting on the bones, kidneys and intestine.

The Actions of Parathyroid Hormone

• An increased level of parathyroid hormone causes their bones to release calcium and the kidneys to reabsorb calcium that would otherwise be lost through the urine. A rise in circulating Ca2+ can then exert negative feedback inhibition on parathyroid hormone secretion.

The Pancreas and Associated Pancreatic Islets

• Alpha cells secrete glucagon and beta cells secrete insulin. The pancreas is also exocrine in function, producing pancreatic digestive enzymes for transport via the pancreatic duct to the duodenum of the small intestine.

Insulin Stimulates Uptake of Blood Glucose

• Binding of insulin to its plasma membrane receptors causes the activation of cytoplasmic signaling molecules which act on intracellular vesicles that contain glucose transporter proteins in the vesicular membranes. This causes the intracellular vesicle to translocate and fuse with the plasma membrane resulting in insertion of the glucose transporters into the plasma membrane and increases glucose uptake from the bloodstream.

Pineal Gland and Melatonin

• The pineal gland is a very small gland that secretes the hormone Melatonin . Melatonin secretion follows a circadian or daily rhythm. This is actually tied to daily and seasonal changes in daylight . Melatonin secretion by the pineal gland begins to increase with darkness and peaks by the middle of the night when you should be sleeping

Secretion of Melatonin

• The secretion of melatonin by the pineal gland is stimulated by sympathetic axons originating in the brainstem. Activity of these neurons is regulated by the hypothalamus which receives input from the retina . Melatonin is inhibited by the retina when light strikes it during the day and is stimulated by lack of light (darkness). 

• Melanopsin is a pigment found in the retina that is not associated with vision but instead controls circadian rhythm activity via melatonin production.