Veterinary Endocrine Physiology

Introduction -

• Textbook: I would recommend getting hold of a copy of Essential Endocrinology (Brook and Marshall) from a library, as the lecturer has obtained most of his diagrams and photos from it… it's basically a human oriented book though, so you probably don't want to buy it.
• Definition: To put the handout definition into context, we can define the following methods of chemical cellular communication: autocrine(cell to same cell), paracrine (cell to neighbouring cells), endocrine (cell to body via general circulation), endocrine with portal system (e.g. the pars distalis of the pituitary), neural, neuroendocrine (e.g. pars nervosa).
• Within the endocrine hormones, we can also define groups of water soluble hormones (proteins, peptides, catecholamines) and fat soluble ones (steroids, thyroxine etc.).
• Water soluble hormonesact on cell surfaces, often through GPCRs, tend to have a relatively short action by altering enzyme activity in target cells (especially by phosphorylation), are concentrated in vesicles in their secreting cells, and are often destroyed by a specific enzyme (especially peptides).
• Fat soluble hormonesact in the nucleus, often altering gene transcription (e.g. steroids). They have a slow onset and long duration of action, and cannot be concentrated in secretory cells. They are usually excreted by the liver following conjugation, and have specific binding proteins in the blood. They use no second messenger systems.
• Main action of the endocrine system is to adopt and maintain appropriate physiological responses to a given environment. They also have important reproductive roles.
• Note that all forms of hormones are seen in the CNS acting as neurotransmitters or neuromodulators (this includes steroid hormones, catecholamines and peptides…)

Signalling Mechanisms -

The Hypothalamohypophyseal Axis -

• Develops embryologically from an outpouching of the third ventricle and Rathke's pouch (which forms in the roof of the buccal cavity). The neural tissue forms the hypothalamus, pituitary stalk and pars nervosa, whilst the pouch produces the pars distalis, tuberalis et intermedia.
• The hypothalamus contains numerous nuclei (which can be identified using immunohistocytology).
• Some of these contain large neurosecretory cells producing the precursors of oxytocin and vasopressin (ADH, also called AVP in many species ('arginine vasopressin' - a few species have variants)). The axons of these cells run down the pituitary stalk and synapse on capillaries in the pars nervosa.
• Others contain small neurosecretory cells producing releasing hormones that synapse on capillaries in the median eminence of the hypothalamus. These then form the portal system that leads to the pars distalis, where the hormones cause cells to release their own hormones. Note that prolactin is inhibited by dopamine release into this system - important for medics (as chronic use of dopamine antagonists can lead to breast development in men), less so for vets as chronic dopamine antagonism is less common.
• The pars distalis produces peptide hormones - FSH, LH and TSH (all closely structurally related), GH and PRL (very similar, single-chain peptides), and ACTH. Many vertebrates release a and b melanocyte stimulating hormones as well, which are derived from alternate cleavage of the precursor protein, proopiomelanocortin [you probably don't need to know about POMC].
• Evidence - take note of the table on page 8 of your lecture notes (I'm not going to copy it out here…). This should be straightforward. Note the pulsatile release of releasing hormones - this complicates measurement.

Regulation of Hormones -

• Most hormones undergo negative feedback (note your handout appears to have incorrect diagrams…)
• Generally, positive feedback only occurs in a limited sense, as it leads to uncontrolled release. Higher brain centres and environmental cues give 'open-loop' positive feedback.
• Endocrine hormones often feed back to reduce their pituitary stimulating hormone, or the releasing hormone - this means that hypersecretion due to a tumour can lead to low levels of the stimulating hormone. This also occurs in Addison's disease - high doses of steroids suppress the release of ACTH by the pituitary, causing atrophy and reduced ACTH responsiveness in adrenal cortex - sudden withdrawal of hormone thus precipitates a crisis (see below).

The Adrenal Gland -

• Often considered part of an axis with the pituitary and hypothalamus. Consist of an inner medulla containing chromaffin cells and a cortex containing three zones - the zona glomerulosa [mineralocorticoids], fasciculata [glucocorticoids] et reticularis [androgens].
• Cortex is supported by ACTH (itself released by CSH). ACTH increases with stress, and this is often taken as a definition of stress in animals. ACTH increases release of glucocorticoids and sex hormones (latter particularly important in e.g. late ovine pregnancy). Cortisol is essential in regulating the immune system through blanket suppression. Glucocorticoids are also needed to effectively concentrate urine (through an unknown, but not same as mineralocorticoid mechanism).
• Medulla supports the role of the sympathetic nervous system during stress (stressed, adrenalectomised animals often undergo circulatory collapse).
• See lecture notes for yet more actions of adrenal hormones, and see end of these notes for some more relevant diseases.

The Thyroid Gland: Thyroxine (T₃) and Tri-iodothyronine (T₄) -

• This is an evolutionarily ancient system. Its role is unclear - we need a change in levels of any hormone to convey information, and yet thyroxine levels always seem to tend towards stability - and changes in secretion often lead to disease. We seem to need a certain amount to 'oil the metabolism'.
• The thyroid gland has a rich blood supply (double that of the kidney per gram), and its cells feature a modified Na/K pump capable of concentrating iodine 250 times. Iodine is also recycled from di- and mono-iodothyronine. T₃ is far more potent, and produced in higher proportion to T₄ during iodine deficiency (apparently simply due to it requiring less iodine). Both hormones are extremely tightly bound to plasma proteins, the extent varying across species.
• Is main control of signal due to differing rates of peripheral deiodination? This could be especially important in the brain - allowing it to maintain a high rate of metabolism compared to the rest of the body, especially during starvation.
• Effects of T₃/T₄ are to increase metabolic rate, body growth, cardiac output; and to alter metabolic pathways.
• Thyroid also produces calcitonin, essential for regulation of plasma calcium levels.
• See below for information about diseases of excess and deficiency in animals.

Other glands -

• NB These are probably not examinable, as they're not in the lecture notes.
• Parathyroid Glands Be aware that the parathyroid glands (four in humans and most [all?] mammals) are embedded in the thyroid, and secrete parathyroid hormone - this hormone acts to increase the conversion of vitamin D into calcitriol, which in turn stimulates calcium and phosphate absorption from the gut. PTH also stimulates osteoblasts (which lay down bone), whilst calcitonin from the thyroid stimulates osteoclasts (which break it down, releasing calcium). See milk fever information below.
• Pancreas Secretes insulin and glucagons (as well as somatostatin) - you have apparently already received lectures on these.
• Reproductive Organs - again, see appropriate lectures.

Vet vs. Medical Clinical Relevance -

• Cushing's disease (hyperadrenocorticism) is found in many species, but with varying age and breed distributions. It is particularly important in dogs and ponies.
• Canine Cushing's Found in middle-aged to old animals, especially poodles. Leads to typical Cushing's symptoms: hair loss, pot belly, polydipsia/uria/phagia, muscle wasting, thin skin. 80-90% of cases are pituitary dependent - generally due to a functional pituitary tumour over-secreting ACTH. Most other cases are due to adrenal tumours, although the disease is occasionally iatrogenic.
  
  


• Equine Cushing's Found in old ponies, generally pituitary dependent. Similar symptoms - excessively hairy coat (long and tangled), sweaty, pot belly. This is also a common cause of chronic laminitis.
  
  


• Thyroid disease is also found in many species.
• Feline hyperthyroidism is the most common form of endocrine disease in cats, and is found most often in older animals. Causes weight loss, polyphagia, irritability and poor coat. These animals can be vicious, and show excessive stalking…
  

Other points of comparison to lecture notes:

• Addison's disease - rare, can be iatrogenic after sudden withdrawal of corticosteroids (as in humans) - aldesterone and glucocorticoid defiency - hard to diagnose, if acute leads to hypovolaemic shock and bradycardia (low aldosterone à Na⁺ loss, K⁺ retention). Autoimmune chronic disease is seen rarely in humans.
• Iatrogenic hypoparathyroidism - seen after removing thyroid tumours in cats to stop hyperthyroidism. Care must be taken with the anatomy here.
• Diabetes mellitus - often seen in older dogs, especially bitches, can be type I/type II (note that this nomenclature is the opposite way round to human forms). Usually either hyposecretion or resistance to insulin, but rarer forms exist.
• Calcium in cows - regulated by parathyroid hormone ['parathormone'], Vitamin D as in humans. Milk fever may arise due to dairy cow milk load overloading homeostatic mechanisms - see special vet physiology. Incidence increases with age. This can be reduced by limiting calcium input during gestation to enhance parathyroid hormone response, then giving vitamin D during parturition - but if this is done too soon, the animal becomes desensitised. Cows lay down extra calcium in bones during their dry periods.