Endocrine Axes & Homeostatic Feedback Flashcards
What is endocrinology in its simplest form?
- Communication between at least three organs (hypothalamus, pituitary gland and peripheral organs)
- First gland sends message
- Second releases hormone into blood
- Third in periphery responds to hormone
What is the purpose of hormones?
- Chemical messengers to respond rapidly to physiological or environmental cues (danger)
- Act on organs and tissues throughout body (regulate internal physiology and behaviour like freeze-fight-flight)
Describe Endocrine glands
-Do not have ducts
=products secreted directly into blood:
=e.g. pituitary, thyroid, adrenal, parathyroid glands, gonads (testis & ovaries)
Describe Exocrine glands
-Products secreted via ducts to epithelial surfaces inside or outside the body:
=e.g. sweat, salivary, mucus, mammary gastric, prostate glands, liver bile duct
How can the pancreas have both endocrine and exocrine functions?
-Endocrine:
=insulin, glucagon, somatostatin & pancreatic polypeptide
-Exocrine:
=digestive enzymes secreted via pancreatic duct to the small intestine
What are the types of endocrine hormone signalling?
-Classical
=Hormone carried by blood
=Receptors on target cells
-Paracrine (local) signalling =Hormone diffuses through tissue fluids =To receptors on target cells-Autocrine (local) signalling =Hormone diffuses through tissue fluids =To receptors on same cell
-Intracrine signalling
=Inactive prohormone enters a cell
=Activated intracellularly (sex steroids like oestrogen)
What are the different types of hormone receptors?
- Peptides (surface receptors- GPCRs or receptor kinases)
- Steroid (cholesterol backbone, less soluble, intracellular, transported on plasma carrier proteins)
- Amine (transported on plasma carrier proteins)
How can hormone receptors be drug targets?
- Steroid receptors= 30% pharma drug targets
- GPCR= 40% pharma drug targets
What are the types of peptide hormones?
-Hypothalamic-releasing hormones
=pass through hypothalamic portal circulation and bind to receptors on specific anterior pituitary cell types)
-Pituitary ‘trophic’ hormones (growth promoting effects)
-Target organ peptide hormones (adrenal medulla catechol-amines acting on vasculature)
Describe peptide hormone action
- Bind to plasma membrane receptors (do not enter cell)
- Act quickly by activating G-proteins
- Generate a chemical second messenger signal (cAMP, Ca2+, protein kinase activation)
What are the classical actions of steroid hormones?
(1) Steroids transported in blood bound to ‘carrier’ proteins.
(2) Diffuse through plasma membrane of target cells bind to inactive cytoplasmic steroid receptors
(3) Activated ‘transcription factor’ enters the nucleus binds to ‘control regions’ activating gene transcription
(4) mRNA leaves the nucleus → new cytoplasmic protein synthesis
* takes time to activate (24-48 hrs)
What is the diffuse endocrine system and what hormones do the organs make?
-Not the classical endocrine glands
- Kidney= RAAS, Ca2+ regulation
- Lungs= RAAS
- Heart= ANP
- Liver= IGF-1/ somatomedin C
- Gut= Leptin, Ghrelin
- Vascular epithelium= endothelin
- Adipose= glucocorticoids
- Skin= stress response hormones
- Salivary glands= growth factors
What is the endocrine axis?
- Hypothalamus + anterior pituitary + endocrine gland + hormone + target tissue
- Hypothalamic releasing hormone= promote release of anterior pituitary hormone= action of distant target gland= target gland response= physiological response
- Hypothalamic- pituitary- target gland axis (thyroid, adrenal, gonad, liver)
Describe homeostasis
-Balance of hormone production and action maintains the internal environment in a balanced state
=hormones released from HP act on target glands to elicit hormone release
=Hormones released from target endocrine glands ‘feedforward’ to target tissues and feedback to inhibit their own production
Describe amplification and degradation of hormones
-Amplification
=’Signalling’ hormones (short half-life only a few mins)
=’End-organ’ hormones (long-lived hours to days)
- Degraded mainly in liver and kidneys (increased in rate in fast metabolism)
- Breakdown products excreted in urine, faeces and bile
What central neural inputs does the hypothalamus coordinate?
-External environment:
=sight, sound, touch, taste, smell, pain, heat, cold , fear (‘freeze, fight or flight’)
-Internal physiology:
=blood pressure, osmolality, blood glucose, hypoglycaemia, starvation chronic pain, fever, inflammation
-Circadian biological clock:
=Suprachiasmatic nucleus (SCN) rhythm generator controls daily endocrine system cycles (entrained by daily light & dark cycle)
Describe the hypothalamus
- Neuroendocrine component of the nervous system within the brain
- Located at the base of the brain
- Linked via the pituitary stalk to the pituitary gland outside the brain
Describe the pituitary gland
-Anterior and posterior pituitary have different embryological origins
-Anterior pituitary:
=blood supply from median eminence
-Posterior pituitary:
=Innervated by hypothalamic axons (extension of CNS)
=oxytocin and vasopressin accumulates
How does the hypothalamus coordinate central neural inputs?
-Stimuli from somatic & visceral sense organs
-Transmitted via sensory & motor neurons from the forebrain and mid brain
-Produce ‘stimulatory’ or ‘inhibitory’ neurotransmitters
=(dopamine, adrenaline, noradrenaline, serotonin, acetylcholine & various neuropeptides)
-Act on distinct hypothalamic ‘nuclei’
=stimulate production of hypothalamic-releasing hormones (peptide synthesis)
What is the median eminence?
- Functional link between the hypothalamus and the anterior pituitary gland.
- On surface of pituitary stalk
- Lies in the centre of the tuber cinereum and is composed of an extensive array of blood vessels and nerve terminals
Describe blood supply to and from the median eminence
- Its extremely rich blood supply arises from the superior hypophyseal artery (a branch of the internal carotid artery), which sends off many small branches that form capillary loops.
- The small capillary loops extend into the internal and external zones of the median eminence, form anastomoses, and drain into sinusoids that become the pituitary portal veins that enter the vascular pool of the pituitary gland.
How is blood supply to the median eminence an advantage?
- The flow of blood in these short loops is predominantly in a hypothalamic-to-pituitary direction.
- This well-developed plexus results in a tremendous increase in the vascular surface area.
- The vessels are fenestrated (no endothelial cells), allowing diffusion of the peptide-releasing factors to their site of action in the anterior pituitary gland.
What is the hypophyseal-portal circulation?
-Because this vascular complex in the base of the hypothalamus and its “arteriolized” venous drainage to the pituitary compose a circulatory system analogous to the portal vein system of the liver, it has been termed the hypophyseal-portal circulation.
What is a portal circulation?
-Two capillary beds joined by a circulation without recycling back into the systemic circulation/ through heart and lungs
