Endocrine system Regulatory systems: endocrine vs nervous Components of the endocrine system Nature of hormones Function of hormones Synthesis, release and regulation of hormones Transportation and removal of hormones Pathologies associated with hormones In the beginning, we know there are endocrine system from pathologies associated

- Like putting hand on hotplate, very fast response Nervous regulation is by specific pathways using specialized high-speed conduction routes (nerves). Therefore effects are usually fast with narrow, specific focus. - Like putting hand on hotplate, very fast response Endocrine regulation is usually via a non-specific pathway, bloodstream, often with a range of targets. Therefore in most cases effects are usually slow. - Long term changes ~ minutes, hours, days - Like spam – where most of the body doesn’t respond to the spam. Only particular individuals would respond There are communication between the two of course.

Endocrine system Regulatory systems: endocrine vs nervous Components of the endocrine system Nature of hormones Function of hormones Synthesis, release and regulation of hormones Transportation and removal of hormones Pathologies associated with hormones

Classic endocrine systems Classic endocrine systems. Cross talk between endocrine and the nervous system. No direct contact from one endocrine gland to the other.

Pituitary – central control, controlled by the hypothalamus somewhat Pituitary – central control, controlled by the hypothalamus somewhat. We don’t talk about the intermediate lobe much, but we think of anterior and posterior. Anterior lobe (LH, FSH) does the gonads. Prolactin – acts on the boobies, not sure what it does in males. GH – acts in liver and bone growth rate and metabolism. ACTH – talks to adrenal gland. Lipotropin & endorphine – they have some significance, but we might not get to em. TSH – controls the thyroid. Posterior Lobe – AVP/ADH – renal function. Oxytocin – small peptide hormone and major function is with birth. Causes contraction of utrine muscle. It doesn’t induce the birt (not natural trigger). Helps propel the fetus out of the uterus. Also involved in expelling milk from the boobies. Unsure what it does in males. Thyroid gland – controlled by TSH. Produces more hormone (layering of control process: hypothalamus > pituitary > TSH > more hormone – complex feedback system to get the required effects) – for body temperature and other control things. PTH – controls free levels of calcium in the body. Consequence calcium goes low, PTH says more calcium. Prevent loss of calcium in the urine and increase absorption of Ca++ in guts and other things. It may eventually take calcium from the bone, until you have no more calcium in the bone! Consequence in osteoporosis. Adrenal Cortex – brings us back to normal if something is taking us away from normal. Steroid hormone. Androgen which give us male characteristics. Cortisol – injury, defense mechanism. Aldosterone – body sodium. DHEA and the androstenedione – kinda ambiguous? Adrenal Medulla - Fight or flight response. Fastest hormonal response, in seconds. Gonads – Testis – estradiol – feminizes. Other hormone – involved in growth control. Ovary - Placenta – involved in birth. hCG – very early after conception. Basis for pregnancy test. hPL – produced by placenta, association with uterus. Development of fetus. Pancreas – major organ where disease process occurs. Insulin – lack of production or lack of response (diabete malletus ~ big problem due to obesity problem). Pineal – melatonin – day & night regulation.

Nonclassical – we don’t talk about these as much. Hypothalamus – produces hormone while comes out and affect other endocrine systems. Leptin – controls appetite? Influences and controls how much we eat.

Endocrine system Regulatory systems: endocrine vs nervous Components of the endocrine system Nature of hormones Function of hormones Synthesis, release and regulation of hormones Transportation and removal of hormones Pathologies associated with hormones

Types of hormone Tyrosine derived Peptide/protein Cholesterol based

Amines – from tyrosine Thyroid – made in various places. Note the iodines, that’s what differentiates T1, T2, T3… etc. Oxytocin – made of AAs… GH – long chain of AAs, insulin is another type Steroids – from cholesterol then modified. Vitamin D – there may be hydroxylation Protein peptides like the water since they are charged, but cannot cross the lipid membrane. Targets must have Extracellular receptors with affinity to these hormones. Induction signaling allows communication to continue. When we make these amine, we store them in granules – and then when we need them, we release them. Amines – two characteristics: 1) We store them in granules 2) they require receptors Thyroid hormones and steroids – different characteristics ~ not soluble in water with all the ring structures. When we make them, we don’t put them in secretory granules. They can cross the lipid membrane and will just leak out. We can’t keep it inside the cell. Once made, it just goes out and cannot be held on. Control process is making the hormone. 90% bound to carrier proteins so they can get to where they need to go. Albumin will carry many of them (like sex steroids). Specific hormone to carry thyroid hormone, or sex hormone, or whatever else. Carrier proteins are required. Carrier proteins have two important functions – 1) to carry stuff 2) to act as a buffer. The effect on the target cell is dictate by not the total amt of hormone in the body, but the amount of free hormone that’s important! Most hormone is bound to these carrier proteins. Sponges! As free hormone goes down, then the sponges will give up the hormones. As free hormone goes up, the the sponges will carry more. Temporarily storage site. When we get to our target ~ hormone that are free – is now happy to go into hydrophobic environment and will go right through the lipid membrane barrier. All the steroid hormone will just go right through. These hormone once inside, brings about physiological response – so they changes whats happening at the nucleus – different protein type production (affects transcription / translation). Cortisol will respond, in cytosol in receptor protein, migrate into nucleus wil then go into part of DNA which is responsive… then changes transcription type… etc.

Cholesterole – where all steroid hormone derived.

Amines – epi and norepinephrine – once they do their things, they break down.

Endocrine system Regulatory systems: endocrine vs nervous Components of the endocrine system Nature of hormones Function of hormones Synthesis, release and regulation of hormones Transportation and removal of hormones Pathologies associated with hormones

Four major functions: Maintaining internal environment Maintaining energy balance Growth and development Reproduction

Maintaining internal environment Fluid balance/electrolytes/volume/blood pressure e.g. ADH, aldosterone, ANF. Plasma calcium/phosphate e.g. PTH, calcitonin, vitamin D. Bone repair and mineralization e.g. PTH, GH, insulin, sex steroids, cortisol.

Maintaining energy balance Utilization of available fuels Storage of surplus fuel Mobilization of fuel stores e.g. insulin, epinephrine, glucagon, thyroid hormone. Storage of energy – to keep the energy steady!

Growth and development Timing and progressions of developmental changes Extent of growth and development of organs and overall body size. e.g. GH, IGF, sex steroids, insulin, thyroid hormones.

Reproduction Growth, development and maintenance of reproductive organs Growth and development of gametes Patterns of sexual behaviour Phenotypic sexual differences Ovulation, spermatogenesis, fertilization, pregnancy, birth and lactation. e.g. GNRH, FSH, LH, estrogen, testosterone, inhibin, progesterone.

Endocrine system Regulatory systems: endocrine vs nervous Components of the endocrine system Nature of hormones Function of hormones Synthesis, release and regulation of hormones Transportation and removal of hormones Pathologies associated with hormones

Synthesis Protein and peptide hormones often made as pre or pro hormones, for secretion and storage, and subsequently proteolytically cleaved to produce the final active hormone. e.g. insulin is synthesized as proinsulin, ACTH is cleaved from pro-opiomelanocortin. Epinephrine and norepinephrine and thyroid hormones derive from tyrosine. Epi and norepi derive directly from enzymic modifications of free tyrosine, whereas the tyrosines for thyroid hormones are iodinated and coupled as parts of a large proteinwhich is subsequently proteolyzed in the thyroid gland.

e.g. cortisol, aldosterone, estrogen, progesterone, testosterone. Steroids all derive from cholesterol which is often taken up in LDLs from the blood by the relevant endocrine glands. E.g. adrenal glands, gonads. Cholesterol enters the mitochondria and is converted by a series of enzymic reactions to the end hormone. The specific end hormone produced depends on the enzymes present in the relevant gland. e.g. cortisol, aldosterone, estrogen, progesterone, testosterone. We store the precursor – the cholesterols. When signal comes in to say we want certain hormone, then we let cholesterol go into mitochondria to make the end product.

Release Protein and peptide hormone are all stored in secretory granules until a relevant signal causes their exocytosis Amine hormones (E and NE) are also stored in secretory granules. Thyroid hormones and steroid hormones are not retained after synthesis and leave the cell directly.

Regulation The circulating levels of most hormones are controlled by feedback loops. These are usually negative feedback loops where the rises in the concentration of an end hormone will result in decreases in earlier components of the control process. More complex control loops also occur. e.g. elevated levels of cortisol shut down ACTH production, rises in testosterone levels decrease LH production.

Endocrine system Regulatory systems: endocrine vs nervous Components of the endocrine system Nature of hormones Function of hormones Synthesis, release and regulation of hormones Transportation and removal of hormones Pathologies associated with hormones

Transportation Many peptide, protein and amine (E and NE) hormones are largely free in the plasma Thyroid and steroid hormones are mostly bound by carrier proteins e.g. thyroxine binding globulin, transcortin, sex steroid binding globulin. Being bound to carrier proteins greatly extends their lifetime in the circulation.

Removal Most active hormones are removed by the liver and kidney. They are often proteolysed or enzymically modified. Breakdown products of protein and peptides can be recycled, whereas much of the metabolites of other hormones enter the urine or bile.

Endocrine system Regulatory systems: endocrine vs nervous Components of the endocrine system Nature of hormones Function of hormones Synthesis, release and regulation of hormones Transportation and removal of hormones Pathologies associated with hormones No questions from here on

Pathologies associated with hormones Pathologies arise from excess (hypersecretion) or insufficiency (hyposecretion) of a hormone (or inappropriate hormone levels for the prevailing conditions). Both of these conditions can arise as the result of primary or secondary disease. Primary disease arises from problems in the gland producing the end hormone. Secondary disease arises from causes outside the gland which lead to changes in the activity of the otherwise normal gland.

Clinical perspective Historically much of what we know about Endocrinology has been based on an understanding of disease states resulting from over-production or under-production of hormones, or from receptor/post-receptor defects.

Giganticism! Before puberty.

Osteoporosis. Drink lots of milk now!

Thyroid gland problem!