Hypothalamus, pituitary and thyroid function

Hypothalamus - an area at the base of the brain

Neurones send axons down from the hypothalamus

To from. The posterior pituitary, a neuroendicrine organ that releases the hormones oxytocin and vasopressin (ADH)

  • the posterior has a neuronal developmental origin as a down-growth from the diencephalon

Anterior pituitary = is ectodermal in origin - developmental origin as an up-growth of ectoderm from the primitive oral cavity

  • neurones in the hypothalamus will send axons to the median eminence

    • Neuropeptide hormones released at the median eminence enter the portal vessels

      • To control the release of hormones from the anterior pituitary

      • Secreted: - GH(growth hormone),

      • FSH - follicles simulating hormon

      • LH - leutinising hormone

      • ACTH - adrenocorticotrophic hormone

      • TSH - thyroid stimulating hormone

      • PL - prolactin

Hormones released from the anterior pituitary enter the venous drainage to reach their target tissues elsewhere in the body.

The main pituitary hormones and their actions

  • posterior

    • Neuronal , releases oxytocin and ADH

  • Anterior

    • Ectodermal - GH, FSH, LH, ACTH, TSH, PL - controls the release of hormones from other glands/ endocrine tissues

Hypothalamus and pituitary

Hypothalamus releases hormones to turn the anterior pituitary on or off. ON = RELEASING HORMONES, OFF= INHIBITNG HORMONES

  • releasing hormones

    • GHRH - growth hormone releasing hormone (cause GH to be released from the anterior pituitary)

    • CRH : corticotropin relasing hormone (stimulates release of ACTH)

    • TRH- Thyotropin rereleasing hormon (stimulate secretion of TSH)

    • GnRH - gonadotropin relasing hormone (stimulates release of LH, FSH)

  • Inhibitory hormones

    • SS: somatostatin (inhibits release of GH, TSH)

    • DA: dopamine - (stops release of PL - prolactin)

Anterior pituitary hormones: FSH/LH

Leutinising and follicle stimulating hormones

  • made in leuteotrophs - gonadotrophs

  • Released in response to hypothalamic GnRH

  • Control production of steroid hormones by the ovary - oestrogen and progesterone

  • Control production of steroid hormones by testis - testosterone

  • Gonadal steroid control sexual differentiation, behaviour and fertility

Loss of FSH/LH secretion

  • loss of function in children stops puberty

  • Extreme calorie deficit in adults - causes loss of reproductive function and loss of FSH/LH

  • Administration of GnRH, FSH/LH can be used to manipulate reproduction

Anterior pituitary : GH

Growth hormones

  • made in somatotrophs

  • Released in response to hypothalamic GHRH

  • Secretion is inhibited by hypothalamic SS

  • Direct anabolic effect in many tissues

  • Targets the liver to produce somatomedins (insulin like growth factor -1/ IGF-1)

  • Somatomedins stimulate growth in many tissues

Lack of GH

  • short statues, can be treated by GH (when young) - before growth plates fuse

Too much

  • giantism - if secreted through growth period

  • Acromegaly - if secreted after bones have fused - causes hands, feet and jaw to grow - due to usually a pituitary adenoma

Anterior pituitary hormone - PRL - Prolactain

  • made in mammotrophs

  • Released when inhibited by hypothalamic dopamine

  • Stimulates lactation in post-partum period

Anterior pituitary hormone : ACTH

  • produced and secreted by anterior pituitary gland

  • Released in response to hypothalamic CRH

  • Acts on the cortex of the adrenal gland to produce and release cortisol

  • Used as a medication (hydrocortisone) in hormone rppacement therapy and to suppress the body’s immune response

Anterior pituitary hormone - TSH

Thyroid stimulating horomr

  • made in throtrophs

  • Released in response to hypothalamic TRH

  • Acts on thyroid to generate Triiodothyronine (T3) and thyroxine(T4)

  • T3 , T4 regulat growth and development by multiple actions

Thyroid hormones and their actions

Thyroid anatomy

  • located in the anterior neck of the trachea, inferior to the larynx

  • Weighs 10-20g, 2 lobes connected by the isthmus

  • Highly vascular - main blood subtly from carotid and subclavian arteries

Thyroid structure and histology:

  • composed of hollow follicles - thyroid follicles

  • Lined by epithelial cells (principal cells) - responsible for the synthesis of thyroid hormones T3/T4

  • Filled with thyroid colloid - which stores T3/T4 before secretion :

  • C-cells -(clear cells, parafollicular cells)

    • Responsible for synthesis and secretion of calcitonin

    • Calcitonin regulates CA2+ homeostasis

What are thyroid hormones

  • amino acids from tyrosine

  • Iodine is essential for the synthesis of thyroid hormones

  • Generated fromiodination and coupling of tyrosine, hence the name TRI-IODOTHYRONNINE(T3) and Tetrea-iodothyronine(thyroxine/T4)

Synthesis and secretion of thyroid hormones

  • follicle (principal cells) make and secrete thyroglobulin into the colloid

  • At the sam time Iodide (I-) is absorbed from the blood into the follicle cells

  • Iodide is oxidised to iodine at the apical membrane, and released into the colloid

  • Iodide attaches to tyrosine, for one mono-iodotyrosine (MIT) or Di-iodotyrosine (DIT) which are incorporated into thyroglobulin (this is catalysed by thyroid peroxidase)

  • Tyrosine-iodide complexes joined together to form T4/T3

  • Colloid endocytosed and combines with lysosome

  • T3/T4 released into capillaries and bind to carrier proteins

Thyroid hormone actions

  • T4/T3 highly bound to serum protens( thyroid binding globulin -TGB) in the circulation less than 0.5% is present in the free form - biologically active

  • T4 - maybe a pro hormone, T3 is th most potent form (10x more active tan T4)

  • T3 is mainly produced by de-iodination of T4 within target cells outside the thyroid gland

  • Once released into circulation - thyroid hormones interact with DNA ad transcription factors and produce changes in gene transcription and protein synthesis

Thyroid receptor - TR/ THR

  • member of hormone responsive nuclear transcription factors

  • Consists of a DNA binding domain and a COOH-terminal domain (mediated ligand interactions and binding of coactivators and corepressors)

  • 2 primary isoforms TR alpha and TR beta

  • TR forms a heterodimer complex with retinoids x receptor (RXR(

Once they form this receptor

TR-retinoids X receprtir (RXR)

  • bind to the thyroid response element TRE

  • Activation of TRE stimulates or inhibits gene transcription

Nuelcear receptor coregulators

  • co activators associate with liganfed nuclear receptors and enhance gene transcription

  • Compressors bind to unliganded preceptors and promote gene repression

Physiological effects of thyroid hormones

  • muscles - increase protein catabolism, increase glycogenolysis

  • Red blood cells - increase RBC formation - enhance oxygen delivery

  • CNS - increase growth and development of nervous system

  • Heart - increase heart rate and force contraction - blood pressure

  • Liver - increase gluconeogeneis, increase glycogenolysis

  • Bones - increase turnover of minerals, linear growth an maturation of bones

Hope is thyroid hormone secretion regulated

  • Classical negative feedback through the hypothalamic-pituitary-thyroid axis

  • Thyrotripin releasing hormone - TRH

    • Produced by hypothalamus

    • Down regulated by T4,T3

    • Stimulates TSH formation

  • Thyroid stimulating hormone - TSH

    • Produced by anterior pituitary

    • Upregulatef by TRH

    • Down regulated by T4,T3

    • Stimulates iodine uptake, colloid endocytosis, nume rand secretory activity, of thyroid cells, therefore secretion of T4,T3]

Thyroid gland disorders

  • underactive - hypothyroidism -

  • Due to thyroid failiure - from birth can do severe developmental abnormalities

  • Can be acquired later in life - lack of iodide in the diet - easily treated with sodium iodide in salt

  • Autoimmune - hashimotos thyroid it is - 1 in 1000 occurrence, 8-15x more in women’s and Middle Ages

  • Circulating antibodies against thyrod peroxidase and or thyroglobulin

  • Symptoms - bradycardia - reduced cardiac output

    • Cold intolerance - decreased BMR

    • Weight ain - decreased BMR

    • Reduction in ATP production

    • Slow mental processes - reduced stimulation of CNS

    • Slow reflexes

    • Muscle wasteing, hair loss, dry skin - decreased protein metabolism

    • Fatigue

    • Lack of T4/T3 means no inhibition of TSH release soo elevated TSH causes thyroid growth - goitres form - lack of negative feedback

  • Lab values -

    • Raised TSH, low T4

    • Precedes of anti-thyroid peroxidase antibody,/ anti-thyroglobulin antibody

    • Increased plasma cholesterol - effect of TH on lipid metabolism

  • Treatment

    • Oral thyroxine - levothyroxine - synthetic T4

    • Oral tri-iodothyronin - more potent but shorter duration

    • Start w low dose 25mcg/ day and slowly increase the dose every 3-4 weeks till TSH is normal

Hyperthyroidims

  • Graves’ disease

  • Most common form

  • Autoimmune disease with antibodies that stimulate the thyroid to secrete T3/T4 agonist antibody

  • Antibody binds to TSH receptor causes excess T3/T4

Symptoms

  • high metabolic rate, weight loss, heat sensitivity

  • Increased cardiac activity

  • Hyperactive nervous system, tremor, anxiety

  • Exopthalamus

Treatment

  • carbimazole or propylthiouracil - inhibit thyroid peroxidase, and decrease thyroid hormone synthesis

  • Propylthiouracil - prevents conversion of T4-T3

  • Partial ablation of the thyroid with surgery or radioactive iodin)(only used if carbimazole has not been effective)

  • B-blocker to counter cardiac effects