Principles of Hormonal Control Systems (Part 6)

Chapter 10 John Paul L. Oliveros, MD, DPPS

Summary of Hormones

Hormone structure and synthesis

3 chemical classes of hormones Amines Peptides and proteins steroids

Amine Hormones Derivatives of

tyrosine Include:

▪ Thyroid hormones▪ Epinephrine▪ Norepinephrine▪ dompamine

Thyroid Hormones Thyroxine (T4) and

Triiodothyronine▪ Secreted by thyroid follicles

Iodine▪ Essential element of thyroid

hormones▪ Food GI tract blood

(converted to iodide) thyroid follicular cells (conversion back to iodine) thyroglobulin (incorportation with tyrosine and thyroglobulin precursor)

Thyroglobulin▪ Found in central spaces between

thyroid follicles▪ Endocytosis into follicular cells

and digested by lysosymes to release thyroid hormones

Thyroid Hormones

Thyroxine (T4) Secreted in large amounts Converted into T3 by most

tissue by deiodination Has no action unless converted

to T3 Persons with defective

deiodination enzyme manifest as thyroid hormone deficiencyeven with normal or increased T4

Triiodothyroxine (T3) More active than T4

Function: Regulation of O2 consumption Growth Brain development and function

Adrenal Medulla Glands and Dopamine

Adrenal gland Adrenal cortex Adrenal medulla▪ Modified sympathetic

ganglion▪ Axons release

secretions into blood (endocrine)

▪ Secrete 2 amine hormones▪ Epinephrine (E)

Secreted 4x more than NE

▪ Norepinephrine (NE)

Dopamine Secreted by cells in

the hypothalamus Function as a

hormone Also secreted by

small amounts in the adrenal glands

Peptide Hormones

Composes majority of hormones

preprohormones (ribosomes) prohormones (endoplasmic reticulum) hormones + peptides (golgi apparatus)

Many also functions as neurotransmitters/ neuromodulators

Steroid Hormones

Produced by the adrenal cortex and gonads, placenta

Cholesterol Steroid produced on a

particular cell depends on the types and concentration of enzymes present

Highly soluble Steroid producing cell

plasma membrane interstital fluid blood binding with plasma proteins

Hormones of the adrenal cortex Aldosterone

Mineralocorticoid Salt (mineral) balance Kidney’s handling of Na+, K+, H+

ions Cortisol and Corticosterone

Glucocorticosteroid Metabolism of glucose and other

organic nutrients Facilitation of response to stress Regulation of immune system

Dehydroepiandrosterone (DHEAS) and Androstenedione Androgens

▪ Include testosterone (testes)▪ Other adrenal androgens function like

testosterone but less potent▪ Play important role in adult female

and both sexes during puberty

Hormones of the adrenal cortex 3 distinct layers of

adrenal cortex Zona glomerulosa▪ High enzyme

concentration to convert corticosterone to aldosterone

Zona fasciculata Zona reticularis▪ Secretes more androgen

and cortisol▪ If less enzyme for

conversion to cortisol, may produce masculinzation in females

Hormones of the Gonads

High concentrations of enzymes to lead to androstenedione

Testes Androstenedione

testosterone Ovaries

High concentrations of aromatase

Androgens estradiol Some ovarian cells

screte progesterone

Hormone transport in blood Concentration of free hormone is more physiologically

important than total concentration

Hormone Metabolism and Excretion

Liver and kidneys Major organs for hormone

excretion and metabolism Target cells

May metabolize cetain peptide hormones

Plasma/blood Rapid elimination of peptide

hormones and catecholamines Less rapid elimination of

protein bound hormones (thyroid and steroid hormones)

Metabolism may activate some hormones instead of inactivating them

Mechanisms of Hormone action Hormone

receptors Ability to respond

depends on the ability of receptors for a homrone on the target cell

Receptors▪ Catecholamines/

peptide hormones▪ Plasma membrane

receptors

▪ Steroid/thyroid hormones▪ Intracellular receptors

Hormone Receptors Permissiveness▪ Hormone A must be

present for the full strength of hormone B’s effect

Mechanisms of Hormone Action Effects of peptide

hormones and catecholamines Activated receptors directly

influence either of the folowing:▪ Ion channels that are part of

the receptor▪ Enzyme activity that is part of

the receptor▪ Acivity of JAK kinases

associated with the receptor▪ G-proteins coupled in the

plasma membrane to effector proteins(ion channels and enzymes) that generate 2nd messengers

Mechanisms of Hormone Action Effect of steroids and

thyroid hormones Steroid hormones,

thyroid hormones, Vit D are closely related

Steroid hormone receptor superfamily

Binding of hormone with receptor causes activation/inhibition of particluar gene change in rate of protein synthesis coded by genes

Inputs that control Hormone Secretion

Most are released in short burst

Some are release in cycles

Controlled mainly by Changes in plasma

concentration of ions and nutrients

Neurotransmitters released from impinging neurons

Another hormone acting on the endocrine cell

In most cases, hormone secretion is influenced by more than 1 input

Inputs that control Hormone Secretion

Control by plasma concentrations of mineral ions or organic nutrients Major function of

hormone is to regulate (negative feedback) the plasma ion or nutrient controlling its secretion

Inputs that control Hormone Secretion

Control by neurons Adrenal medulla

behaves like a sypathetic ganglion

Other endocrine glands controlled by autonomic nervous system

Examples:▪ Insulin▪ Other gastrointestinal

hormones

Inputs that control Hormone Secretion

Control by other hormones Secretion of a

particular hormone is directly controlled by the blood concentration of another hormone

Trophic hormone▪ A hormone that

stimulates the secretion of another hormone

▪ Usually stimulate growth of the stimulated gland

Control Systems Involving the Hypothalamus and Pituitary

Pituitary gland Anterior pituitary▪ AKA adenohypophysis▪ With hypothalamo-pituitary

portal vessels▪ Local route for blood flow

directly from hypothalamus to anterior pituitary

Posterior pituitary▪ AKA neurohypophysis▪ Outgrowth of the

hypothalamus▪ Neural tissue▪ Axons that end near posterior

pituitary from hypothalamic nucleus▪ Supraoptic nuclei▪ Paraventricular nuclei

Posterior Hypothalamus

Hormones secreted are synthesized in the hypothalamus

Hormones travel to posterior pituitary enclosed in small vesicles

Stimuli (hormones/neurotransmitter) action potentials axon terminals exocytosis of hormones

2 posterior pitutary hormones Oxytocin▪ Acts on smooth

muscles in breast and uterus

Vasopressin▪ AKA anti-diuretic

hormone▪ Control of water

excretion by the kidneys

▪ Control of blood pressure

The hypothalamus and anterior pituitary

Hypophysiotropic hormones AKA hypothalamic

releasing hormones Hormones from the

hypothalamus that influence the anterior pituitary

1st of the 3 hormone sequence▪ Hypophysiotropic

hormone▪ Anterior pituitary hormone▪ Endocrine gland hormone

Anterior Pituitary Hormones Anterior pituitary secretes 8

hormones Only 6 functional/classical

hormones Follicle-Stimulating Hormone (FSH) Luteinizing Hormone (LH) Growth Hormoe (GH) Thyroid stimulating hormone

(TSH/thyrotropin) Prolactin Adrenocorticotropic hormone

(ACTH/corticotropin) Gonadotropic hormones

FSH LH

2 peptide hormones with unknown functions B-lipotropin B-endorphin

Hypophysiotropic Hormones Hypothalamic hormones that

regulate secretion of anterior pituitary hormones

Axons that secrete these hormones terminate in the median eminence around the hypothalamo-pituitary portal vessels

Difference with posterior pituitary hormone Neurons remain at the

hypothalamus, ending at its median eminence

Hypophysiotropic hormones enter median eminence capillaries hypothalamo-pituitary portal vessels anterior pituitary hormone▪ Anterior pituitary exposed to high

concentrations of hypophysiotrophic hormones

Hypophysiotrophic hormones

Hypophysiotrophic Hormones

Hypophysiotropic Hormones Neural control

Hypothalamus receive synaptic input from virtually all areas of the CNS

Large number of neurotransmitters are relased on synapses of hormone secreting hypothalamic neurons

Secretion of hypophysiotropic hormones can be influenced by drugs that influence neurotransmitters

Hypophysiotropic Hormones Hormonal Control of the

hypothalamus and anterior pituitary Negative feedback

(prominent feature of each sequence)

Effectivein dampening hormonal response / limiting extremes of hormonal secretory rates

Maintain plasma concentrations of the final hormone in a sequence constant whenever a disease-induced primary change occurs in the secretion or metabolism of the hormone

Hypophysiotropic Hormones Long-loop negative

feedback 3rd endocrine gland exerts

negative feedback effect on the hypothalamus/anterior pituitary gland

Exists on each of the 5 three-hormone sequences initiated by a hypophysiotropic hormone

Short-loop negative feedback influence of an anterior

pituitary hormone on the hypothalamus

Role of “nonsequence” hormones on hypothalamus/anterior pituitary

Hormone that is not itself in a particular sequence influences hypothalamus and anterior hormone secretion

e.g. Estrogen enhances secretion of prolactin

Candidate Hormones

Suspected hormones in humans butare not considered as classical hormones because Functions have not been

conclusively documented Have well documented

function in as paracrine/autocrine agent

Not certain if they reach target cell via blood

Melatonin▪ Produced by the pineal

gland▪ Probably important in the

setting of the body’s circadian rythms and sleep

▪ Ability to reduce jetlag▪ Relationship to seasonal

affective disorder (“winter depression”)

▪ Potentials:▪ Natural sleeping pill▪ Scavenge free radicals▪ Control of the reproductive

system

Endocrine Disorders

Types: Hyposecretion▪ Too little hormone

Hypersecretion▪ Too much hormone

Hyporesponsiveness▪ Reduced response of

target cells Hyperresponsivenes

s▪ Increase response of

target cells

Hyposecretion Primary hyposecretion▪ Gland is not able to

function normally▪ Examples:▪ Decrease cortisol due to

genetic absence of a steroid -forming enzyme in adrenal cortex

▪ Decrease thyroid hormones due to dietary deficiency of iodine

▪ Damage of an ndocrine gland due to: Infection Toxic chemicals

Endocrine Disorders

Hyposecretion Secondary hyposecretion▪ Gland secreting too little

hormonebecause there is not enough tropic hormone

▪ Example:▪ Decreased TSH (ant.

Pituitary) decreased thyroid hormone

Tertiary Hyposecretion▪ Decreased hormone

secretion from hypothalamus▪ Example:▪ Dec TRH dec TSH dec

thyroid hormones

Hyposecretion: Diagnosis▪ Determine concentration of a

hormone in the plasma or urine▪ Measure concentration of a

tropic hormone to distinguish between primary and secondary hyposecretion

▪ Administering tropic hormone or substance known to elicit secretion of a hormone▪ Primary defect: less than

normalincrease in hormone▪ Secondary defect: normal

increase in hormone

Treatment▪ Administering missing or

deficient hormone

Endocrine Disorders

Hypersecretion Primary hypersecretion

▪ Gland secreting too much of the hormone on its own

▪ Most common cause:▪ Hormone-secreting

endocrine cell tumor

Secondary hypersecretion▪ Excessive stimulation of a

gland by its tropic hormone

Tertiary hypersecretion▪ Hypersecretion of a

hypophysiotropic hormone (hypothalamus)

Hypersecretion Diagnosis

▪ Measure concentration of a hormone and its tropic hormone (blood/urine)

▪ Secondary hypersecretion▪ Concentration of both hormone and

topic hormone elevated

▪ Primary hypersecretion▪ Decreased secretion of a tropic

hormone because of negative feddback

▪ Tertiary hypersecretion▪ Increase in hypophysiotropic hormone

Treatment▪ Surgical removal or radiation

destruction of a endocrine tumor▪ Inhibitory drugs on hormon’s

synthesis▪ Drugs that block hormone’s effect on

target cells

Endocrine Disorders

Hyporesponsiveness Target cells do not

respondnormally to a hormone Types

▪ Deficiency of receptors for the hormone

▪ Events after hormone binding is defective

▪ Lack or deficiency of enzymes that catalyzes activation of a hormone

Diagnosis:▪ Plasma concentration of hormones

are normal or elevated despite diminished response of target cells

Examples▪ Diabetes mellitus (sugar diabetes)▪ Target cells are hyporesponsive to

insulin

Hyperresponsiveness Thyroid hormone cause up-

regulation of certain receptors of epinephrine▪ Tachycardia in hyperthyroidism

The End