PNB 3270 Introduction to Molecular Endrocrinology

Bioregulation

- the maintenance of homeostasis by means of signaling throughout the body

- includes: the endocrine system, the nervous system, and the immune system

Bioregulators

chemicals involved in biological systems

molecular endocrinology

studies of structures, synthesis and actions of hormones (bioregulators) at cellular and molecular levels

Classic definition of a hormone

Hormones are chemical substances produced by specialized tissues (endocrine glands) and secreted into the blood stream, where they are carried to target organs to produce a desired effect

Broader definition of a hormone

hormones are chemical, non-nutrients, intracellular messengers that are effective at micromolar concentrations or less. In other words, hormones are chemical substances that carry information between two or more cell types. They are also called "bioregulators."

Discrepancies between the classic (hormones) and the broader (bioregulators) definitions

- specialized tissue for hormone synthesis vs. multiple tissues

- blood for hormone distribution vs. blood, intercellular fluid

- a separate organ for hormone action vs. multiple target tissues

Categories of Bioregulators

1. Neurocrines (neurotransmitters or neuromodulators)

2. Neurohormones

3. Hormones

4. Autocrine/paracrine regulators

5. Ectohormones (semiochemicals

Neurotransmitter

secreted by neurons into synaptic space

Examples of Neurotransmitters

Acetylcholine, dopamine, substance P, GABA

neuromodulator

Secreted by neurons into synaptic space; modulates sensitivity of postsynaptic cell to other neurotransmitters

examples of neuromodulators

endorphins and various other neuropeptides

Neurohormone

secreted by neurons into the blood or CSF; may be stored in neurohemal organ prior to release

examples of neurohormones

TRH, CRH, oxytocin, dopamine

examples of hormones

Thyroxine, GH, insulin

cytocrine

- secreted by cells into surrounding extracellular fluid; these local regulators typically travel short distances to nearby target cells

- include growth factors, mitogenic regulators, embryonic tissues-inducing substance

- can act as autocrines or paracrines

examples of cytocrines

somatostatin, norepinephrine

paracrine

secreted by cells that affect other cell types

examples of paracrines

embryonic inducers, somatostatin, interleukins

Autocrine

secreted by cells that affect emitting cells

examples of autocrines

mitogenic agents, interleukins

Intracrine

- Intracellular messengers; typically mediators of other regulators that bind to membrane receptors

- govern intracellular events

- secondary messengers or transcription factors

examples of intracrines

cAMP, DAG, IP3, cGMP, calmodulin, calcium ions

semiochemicals/ectohormones

secreted into the environment

examples of semiochemicals/ectohormones

Pheromones, allelomones

Pheromones

act only on the same species

ex. ant trail pheromones

Allelomones

act on different species

1. allomone: benefit own species (snake venom, skunk spray)

2. Kairomone: benefit recipient species (sweat has 1-lactate which attracts mosquitos for feeding)

Regulator classes

Nonpeptides

Hypothalamic-releasing peptides

Other neuropeptides

Acetylcholine

nonpeptide

Carbon monoxide

nonpeptide

Dopamine

nonpeptide

Epinephrine

- nonpeptide

- amino acid derivative

Gamma-aminobutyric acid (GABA)

nonpeptide

Glutamate

nonpeptide

Nitric oxide

nonpeptide

norepinephrine

nonpeptide

serotonin

nonpeptide

Corticotropin-releasing hormone (CRH)

- hypothalamic-releasing peptide

- Promotes secretion of adrenocorticotropic hormone (ACTH)

Gonadotropin-releasing hormone (GnRH)

- hypothalamic-releasing peptide

- Promotes secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH)

melanotropin-releasing hormone (MRH)

-hypothalamic-releasing peptide

-a hexapeptide that stimulates the secretion of melanotropin

Prolactin Releasing Hormone (PRH)

- hypothalamic-releasing peptide

- stimulates secretion of prolactin

Prolactin release-inhibiting hormone (PRIH)

- hypothalamic-releasing peptide

- inhibits the secretion of prolactin

Somatostatin (SS)

hypothalamic-releasing peptide

Thyrotropin-releasing hormone (TRH)

- hypothalamic-releasing peptide

- peptide hormone

- Promotes secretion of thyroid-stimulating hormone (TSH) and prolactin (PRL)

Angiotensin II

neuropeptide

arginine vasopressin (AVP)

neuropeptide

targets the kidney for water reabsorption

Atrial natriuretic peptide (ANP)

neuropeptide

Brain Natriuretic Peptide (BNP)

neuropeptide

Cholecystokinin

neuropeptide

Insulin

- neuropeptide

- A protein hormone secreted by the pancreas that is essential for the metabolism of carbohydrates and the regulation of glucose levels in the blood.

Neuropeptide Y (NPY)

neuropeptide

Neuropeptide YY (PYY)

neuropeptide

Peptide histidine isoleucine (PHI)

neuropeptide

Substance P

neuropeptide

Vasoactive Intestinal Peptide (VIP)

neuropeptide

duodenal hormone that stimulates buffer secretion, inhibits acid production, and dilates intestinal capillaries

Exocrines

bioregulators secreted by exocrine glands into ducts through which the secretions are conveyed to their sites of action on the free surface of the epithelium (digestive tract, reproductive tract, or skin)

Peptide and protein hormones

-Most abundant class of chemical messengers

-Consist of specific amino acids

-Hydrophilic

-Chains of amino acids

-peptides (< 50 amino acids)

-proteins (> 50 amino acids)

-TRH (shortest peptide hormone - 3 amino acids long), GnRH, GH, PRL, insulin

amino acid derivative hormones

-derived from 1 or 2 amino acids w/ additional modifications

-Include epinephrine, norepinephrine, and thyroid hormone

-Have names that end in -in or -ine (thyroxine)

steroid hormones

-derived from cholesterol

-produced by gonads and adrenal cortex

-Bind to intracellular receptors

-function by binding to DNA to alter gene transcription

-Slower and longer lived (have direct actions on DNA)

-Not water soluble --> must be carried by proteins in bloodstream --> inactive while attached to carrier protein (must dissociate from carrier to function)

-Have names that end in -one, -ol, or -oid (testosterone, cortisol, glucocorticoids, estrogen, cortisone)

Lipid Hormones

prostaglandin

retinoic acid

etc.

synthesized on smooth ER

Nucleotides

cAMP, cytokinins, 1-methyladenine etc.

Oligosaccharides

short chains of 3 or more monosaccharides (at least 10)

alpha-1,4-oligogalacturonide

Gas bioregulators

CO, NO, ethylene

Cortisol

- a steroid hormone

hydrophobic

- stress hormone

Prostaglandin

lipid molecule that has hormone-like effect; tissue hormone

platelet activating factor

Inflammatory mediator generated from a complex lipid stored in cell membranes.

alpha-1,4-oligogalacturonide (an elicitor)

an oligosaccharide

Zeatin

a cytokinin

--> a nucleoside

ethylene

A gaseous plant hormone that promotes fruit ripening and opposes auxins in its actions

steroid secreting cells

abundance of SER >> stains with eosin producing a pink cytoplasm

Lipid vacuoles do not stain >> appear as small clear openings in cytoplasm

mitochondria with tubular cristae

Growth hormone secreting cells

vesicle-like secretions

dense secretory granules, well-developed Golgi apparatus, and mitochondria with plate-like cristae

merocrine secretion

- secretions released by vesicle exocytosis - most common

- often continuous

eg sweat, pancreatic cells, saliva, enzymes

apocrine secretion

- sloughing of apical portion of secretory cells

- partial cell breakdown

- cytoplasm and vesicular contents secreted

- arm pit sweat, mammary glands (milk)

Holocrine secretion

- release through cell death and lysis

- entire cell lost with secretion

- cells fill up with secretion and burst releasing cytoplasmic contents

- stem cells divide and replace lost cells

- ex. sebaceous (oil) glands

Cytogenous Secretion

release of whole, viable cells

ex. sperm or ova release

1.

Hypothalamus

2.

Pituitary

3 a.

Endocrine glands

1. HP-A axis: Hypothalamus-Pituitary-Adrenal axis

2. HP-L axis: Hypothalamus-Pituitary-Liver axis

3. HP-G axis: Hypothalamus-Pituitary-Gonad axis

4. Hypothalamus-Pituitary-Thyroid axis

3 b.

Endocrine glands independent of HP axis

pancreas: insulin and glucagon parathyroid gland: PTH

kidney: renin and erythropoietin

adipose tissues: leptin

4.

target organs

5.

effect

6.

nonapeptide hormones

oxytocin

vasopressin

neuroendocrine system

brain (hypothalamus) and pituitary gland (producing tropic hormones and other hormones)

Tropic hormones

Hormones secreted by the pituitary glands that regulate the secretion of hormones from classic endocrine glands

classical endocrine glands

thyroid gland, adrenal glands, gonads, and liver

independent endocrine glands

parathyroid glands, thymus, endocrine pancreas, organs of the gastrointestinal tract, pineal gland, and the kidney

Hypothalamus

- producing hypothalamus releasing neurohormones such as TRH, GnRH, GHRH, GH-RIH, PRIH, PRH, MRIH, MRH

- producing other neurohormones such as AVP, OXY, Endophines/enkephalins

Growth hormone-releasing hormone (GHRH)

-Promotes secretion of growth hormone (GH) from anterior pituitary

- Hypothalamus

Growth hormone-release inhibiting hormone (GH-RIH)

- Inhibits the secretion of growth hormone (GH) from anterior pituitary

- Hypothalamus and Endocrine Pancreas

melanotropin-release inhibiting hormone (MRIH)

hypthalamus

inhibits release of melantropic

arginine vasopressin

- is involved in raising blood pressure.

- hypothalamus

- nonapeptide hormone

oxytocin

- A hormone released by the hypothalamus that stimulates uterine contractions during childbirth and milk ejection during breastfeeding.

- nonapeptide hormone

enkephalins and endorphins

- Two neurotransmitters that act like *opiates* to block pain.

- hypothalamus

anterior pituitary

- producing glycoprotein tropic hormones such as TSH, LH, and FSH

- producing nonglycoprotein tropic hormones such as GH, PRL, ACTH, and MSH

Thyroid Stimulating Hormone (TSH)

- stimulates secretion from thyroid gland

- stimulated by TRH

- anterior pituitary

- glycoprotein tropic hormone

Leutinizing Hormone (LH)

- stimulates ovaries/testes to start producing sex hormones

- stimulated by GnRH

- anterior pituitary

- glycoprotein tropic hormone

Follicle-stimulating hormone (FSH)

- stimulates production of ova and sperm

- stimulated by GnRH

- anterior pituitary

- glycoprotein tropic hormone

Growth Hormone (GH)

- stimulates all tissues to grow and metabolize nutrients

- stimulated by GHRH

- inhibited by GH-RIH

- anterior pituitary

- nonglycoprotein tropic hormone

Prolactin (PRL)

- stimulates mammary glands to secrete milk

- stimulated by PRH

- inhibited by PRIH

- anterior pituitary

- nonglycoprotein tropic hormone

Adrenocorticotropic hormone (ACTH)

- Stimulates adrenal cortex to secrete glucocorticoids (cortisol)

- stimulated by CRH

- anterior pituitary

- nonglycoprotein tropic hormone

Melanotropin (MSH)

- stimulates melanocytes to produce and release melanin

- stimulated by MRH

- inhibited by MRIH

- anterior pituitary

- nonglycoprotein tropic hormone