Hypothalamus, pituitary and thyroid function

describe the anatomy of the hypothalamus and pituitary gland

-              The hypothalamus is an area at the base of the brain

-              Neurones send axons down from the hypothalamus to form the posterior pituitary (a neuroendocrine organ)

-              The posterior pituitary gland secretes oxytocin and vasopressin (ADH)

-              These hormones are synthesised at the hypothalamus but stored in the posterior pituitary gland

-              The anterior pituitary is ectodermal in nature (derived from Rathke’s pouch, part of the mouth which develops in the foetus and loses connection at some point to form the anterior pituitary gland)

Where do neurones in the hypothalamus go to?

o   Neurones in the hypothalamus send axons to the median eminence, where neuropeptides are released

§  These neuropeptides enter the portal vessels to control the release and synthesis of hormones from the anterior pituitary gland (these can be stimulatory or inhibitory)

§  Hormones released from the anterior pituitary gland enter the venous drainage to reach the target tissue via blood

what hormones does the anterior pituitary gland secrete?

§  Growth hormone

§  FSH

§   LH

§  Adrenocorticotrophic hormone (ACTH) – regulates cortisol from the adrenal gland

§  Thyroid stimulating hormone (TSH)

§  Prolactin

It is ectodermal

what does the posterior pituitary gland secrete?

oxytocin and ADH

It is neuronal

what happens at the median eminence?

-              Stimulatory neurohormones at the median eminence – releasing hormones at anterior pituitary

what are the stimulatory neurohormones?

o   Growth hormone releasing hormone (GHRH)

o   Corticotropin releasing hormone (CRH) – stimulates release and synthesis of ACTH

o   Thyrotropin releasing hormone (TRH) – stimulates release and synthesis of TSH

o   Gonadotropin releasing hormone (GnRH) – stimulates release and synthesis of LH and FSH

what are the inhibitory neurohormones at the median eminence?

o   Somatostatin (SS) – inhibits GH and TSH

o   Dopamine (DA) – inhibits PL

what controls the release of FSH and LH?

GnRH

where is FSH and LSH made?

o   made in luteotrophs (gonadotrophs)

o   These also control the release of the steroid hormones oestorgen and progesterone in the ovaries and testosterone in the testis

what does FSH and LH control?

control sexual differentiation, behaviour and fertility

what occurs if there is a loss of FSH or LH secretion?

§  Prevents puberty

§  Can occur due to calorie restriction in adults due to eating disorders or excessive exercise = loss of reproductive function

§  Administration of FSH/LH or GnRH can manipulate reproductivity

where is growth hormone made?

somatotrophs

when is growth hormone released and inhibited?

o   Released in response to hypothalamic GHRH but can be inhibited by hypothalamic SS

what is the effect of growth hormone secretion?

o   Has a direct anabolic effect in many tissues

o   Targets the liver to produce somatomedins (insulin-like growth factor 1)

Somatomedins stimulate growth in many tissues

what occurs if there is a lack of GH?

§  Short stature (treated by giving GH)

what occurs if there is too much GH?

§  Gigantism – overproduction of GH before bones have fused

§  Acromegaly – overproduction of GH after bones have fused. Usually causes large face, hands, feet (usually caused by a pituitary adenoma, a benign non-cancerous tumour)

where is prolactin made?

mammotrophs

what is prolactin release inhibited by?

hypothalamic dopamine

what is adrenocorticotropic hormone (ACTH) produced and secreted by?

anterior pituitary gland

when is ACTH released?

o   Released in response to hypothalamic CRH (corticotropin releasing hormone)

what is the role of ACTH?

o   ACTH acts of the cortex of the adrenal gland to produce and release cortisol

§  Can be used as medication (hydrocortisone) in HRT and to suppress the immune response

where are the thyroid hormones TSH made?

thyrotrophs

when is TSH released?

in response to TRH

what does TSH do?

Acts on the thyroid gland to generate triiodothyronine (T3) and thyroxine (T4) – these both regulate growth and development

describe the anatomy of the thyroid gland

o   Located in anterior neck on the trachea, inferior to the larynx

o   Formed of two lobes connected by the isthmus

o   Highly vascularised (supply from carotid and subclavian arteries)

what is the function unit of the thyroid called? Describe their properties

o   Functional unit of thyroid – thyroid follicle

§  These follicles are hollow and lined with principal epithelial cells (Responsible for the secretion of T3 and T4

§  Thyroid colloid stores T3 and T4

§  Clear cells (C cells and parafollicular cells) – synthesise and secrete calcitonin, which regulates Ca2+ homeostasis

what type or hormone are thyroid hormones?

-              They are amino acid hormones derived from tyrosine

what is essential for the synthesis of thyroid hormones?

iodine

-              Iodine is essential for the synthesis of thyroid hormones

-              Generated from the iodination and coupling of tyrosine

what can a lack of iodine lead to?

-              cause hypothyroidism due to a lack of production of T3 and T4

how are thyroid hormones synthesised and secreted?

o   Principal/follicle cells synthesise and secrete thyroglobulin into the colloid

o   Iodide is absorbed from the blood into the follicle cells

o   Iodide is oxidsed to iodine at the apical membrane and is released into the colloid

o   Iodine attaches to tyrosine, forming mono-iodotyrosine (MIT) or di-iodotyrosine (DIT), which are incorporated into thyroglobulin (this process is catalysed by thyroid peroxidase)

o   These complexes join to form T3 + di-iodotyrosine + mono-iodotyrosine OR T4 + 2x di-iodioyrosine

o   Endocytosis occurs at the colloid and it is combined with a lysosome

o   T3 and T4 is released into the capillaries and bind to carrier proteins

o   Due to this binding, only 0.5% of T3 and T4 is unbound and therefore biologically active

which of T3 and T4 is more active?

o   T3 is up to 10x more active than T4, so T4 may be a pro-hormone

where are thyroid hormone specific receptors found?

are found in the nucleus so, can interact with DNA as transcription factors to influence transcription and translation

describe the properties of the thyroid receptor TR/THR

-              consists of a DNA binding domain and COOH terminal domain

o   Has two isoforms

o   Thyroid receptor can form a complex with a retinoid receptor

§  This complex can bind to the thyroid response element (TRE) whereby activation of TRE can inhibit or stimulate gene transcription

§  This process is also aided by nuclear receptor coregulators

·      Coactivators associate with liganded nuclear receptors (thyroid receptor) and enhances gene transcription

·      Corepressors bind to unliganded receptors and promote gene repression (aka turning off the gene)                 

what is the effect of thyroid hormones on the CNS?

increase of growth and development of NS

what is the effect of thyroid hormones on the heart?

Increases bpm and force of contraction and therefore mmHg

what is the effect of thyroid hormones on the liver?

Increases gluconeogenesis and glycogenolysis

what is the effect of thyroid hormones on the bones?

Increases turnover of minerals, causing linear growth and maturation of bone

what is the effect of thyroid hormones on endocrine tissue?

increases activity

what is the effect of thyroid hormones on RBC’s?

Increases cell formation and enhances oxygen delivery

what is the effect of thyroid hormones on muscles?

increases protein catabolism and glycogenolysis

how is thyroid hormone secretion regulated?

-              Negative feedback via hypothalamic pituitary thyroid axis (HPT)

-              An increase in basal metabolic rate will downregulate or inhibit TRH and TSH, so less thyroid hormone is produced

describe the properties of thyrotropin releasing hormone TRH

o   Produced by hypothalamus

o   Down regulated by T4 and T3

o   Stimulates TSH formation

describe the properties of TSH

o   Produced by the anterior pituitary gland

o   Upregulated by TRH

o   Downregulated by T4 and T3

o   Stimulates iodine uptake, colloid endocytosis, number and secretory activity and therefore secretion of T3 and T4

what is thyroid failure?

-              congenital (from birth) and can produce severe developmental abnormalities if untreated OR in adult life due to lack of iodide in diet (leads to hypothyroidism)

what is hashimotos’s thyroiditis?

-              autoimmune destruction of thyroid

o   Circulating antibodies against thyroid peroxidase /thyroglobulin

what are the symptoms of hypothyroidism?

o   Bradycardia (reduced CO)

o   Cold intolerance (decreased BMR)

o   Weight gain (decreased BMR)

o   Slow mental processes (reduced stimulation of CNS)

o   Slow reflexes

o   Muscle wasting, hair loss, dry skin (decreased protein metabolism)

o   Fatigue

o   Lack of T3 or T4

o   Thyroid goitres form

§  Lack of negative feedback due to decreased T4 and T3 so, elevated TSH = thyroid growth

what blood results would you see for hypothyroidism?

raised TSH, low T4, presence of autoimmune anitbodies against thyroid peroxidase and thyroglobulin, increased cholesterol)

what treatment is given for hypothyroidism?

o   Life long levothyroxine (synthetic T4) – start at low dose and slowly raise until TSH is normal

o   Oral tri-iodothyronine (more potent than levothyroxine but not shorter acting)

what is Grave’s disease?

-              hyperthyroidism (most common form of hyperthyroidism)

o   An autoantibody is generated which stimulates the secretion of T3 and T4

what are the symptoms of hyperthyroidism?

§  High metabolic rate (heat sensitivity, weight loss

§  Increased cardiac activity

§  Hyperactive nervous system, tremor, anxiety

§  Exopthalamus (bulging eyes)

what is the treatment for hyperthyroidism?

§  Carbimazole or propylthiouracil – inhibits thyroid peroxidase and decreases synthesis of TH

§  Propylthiouracil prevents conversion of T4 to T3

§  Can surgically remove some of the thyroid

§  Can use Beta blockers for racing heart symptoms