The Hypothalamus and Pituitary Gland

Hello :) This is the first post of the Endocrinology section of our second Veterinary Physiology unit this year. Today we'll have a look at how hormones are classified, as well as the anatomical features of the anterior and posterior pituitary gland. We'll also discuss ADH and oxytocin as well as diabetes insipidus.

Hormone Classification

Hormones can be classified into three groups according to how they reach their target cells:

• Classical Hormones: these are carried by the blood to the target cells from endocrine cells. 
• Neurohormones: These are released from neurons and are carried by the blood to their target cells as classical hormones. 
• Local Hormones: These act on target cells in the immediate vicinity and two types exist:
• Paracrines: which act on neighbouring cells
• Autocrines: which act on the secretory cell itself.

  Hormones can also be classified according to their structure:

• Amine Hormones: These are derivatives of single amino acids and include thyroid hormones and catecholamines (adrenaline and noradrenaline)
• Peptides and Polypeptide Hormones: These are synthesised as larger, non-active preprohormones. This means that they have an "extra bit" attached to the hormone which is later removed in order for the hormone to work. Importantly, these hormones are water soluble and so don't need transport proteins to get to their target cells - they can dissolve in blood plasma. 
• Steroids: These are lipid molecules derived from cholesterol and include glucocorticoids (such as cortisol), mineralocorticoids (aldosterone) and androgens (testosterone). These hormones are not soluble in water and need to be transported in the bloodstream bound to proteins.

The Hypothalamus and Pituitary Gland

These two structures are very important as together, they regulate almost every system in the body. The hypothalamus is connected to the pituitary by a stalk of tissue known as the infundibulum. The pituitary gland is divided into two lobes:

• the Anterior lobe (aka. the adenohypophysis)
• the Posterior lobe (aka. the neurohypophysis)

The hypothalamus receives sensory information from both the internal and external environment and regulates body activities through the autonomic nervous system and endocrine system. The hypothalamus contains nerve cell bodies which synthesise hypophysiotrophic (hormones which regulate the anterior pituitary only) releasing and inhibiting hormones to communicate with the anterior pituitary. The nerve cell bodies also synthesise the neurohypophyseal hormones of the posterior pituitary.

Anterior Pituitary (AP)

The hypothalamus and AP synthesise and release tropic hormones (hormones that regulate the release of other hormones) which may be stimulatory or inhibitory. The hypothalamus and AP are connected by two capillary beds in series, this is called the Hypothalamic-Pituitary Portal System. The process of releasing a hormone is as follows:

1. Tropic hormones are synthesised in the hypothalamic neurosecretory cells. 
2. Neural stimulation causes these hormones to be secreted into the 1st capillary bed.
3. They then travel to the pituitary gland in a portal vein.
4. The hormones enter the 2nd capillary bed at the anterior pituitary. 
5. Here they stimulate/inhibit the release of anterior pituitary hormones. 

The hypothalamic-pituitary portal system is a closed system and so the products secreted here do not enter the general circulation. This allows them to reach high concentrations as they are not diluted. The hormones are also delivered directly to the AP allowing them to have a greater effect on hormone release. Below is a diagram showing the hypophysiotropic hormones and their effects on the anterior pituitary and subsequently the tissues of the body.

Hypophysiotropic Hormones

Clicking the diagram should enlarge it so it is easier to read.

Key: 

GnRH = Gonadotropin Releasing Hormone       GHRH = Growth Hormone-Releasing Hormone

SS = Somatostatin     GHIH = Growth Hormone Inhibiting Hormone     TRH = Thyrotropin-Releasing Hormone   PRH = Prolactin-Releasing Hormone    DA = Dopamine   CRH = Corticotropin-Releasing Hormone   LH = Luteinising Hormone    FSH = Follicle Stimulating Hormone     GH = Growth Hormone     TSH = Thyroid Stimulating Hormone    ACTH = Adrenocorticotropic Hormone

Posterior Pituitary (Neurohypophysis)

The posterior pituitary (PP) is not a true endocrine gland as it doesn't synthesise its hormones. The PP consists of axonal processes and termini of neurosecretory cells of the hypothalamus. These are the supraoptic and paraventricular nuclei. The neurosecretory cells of the hypothalamus synthesis ADH (anti-diuretic hormone, also called vasopressin) and oxytocin which are stored at the PP. 

Oxytocin and ADH

Synthesis and Storage: Both oxytocin and ADH are synthesised in the supraoptic and paraventricular nuclei of the hypothalamus. Both are stored in the nerve terminals of within the PP. Prohormones are synthesised in hypothalamic neurosecretory cells and are packaged into secretory vesicles. This means that oxytosin and ADH are bound to protein carrier molecules (neurophysin I and neurophysin II respectively) These vesicles are stored at neuron terminals within the PP. Following a neural signal the hormone is cleaved and released by exocytosis into the general circulation. 

Signals for Release: Three different signals may cause oxytocin to be released:

1. Sensory mechanoreceptors during suckling or udder massage prior to milking
2. Stretch receptors in the cervix
3. visual/auditory stimuli of the calf. 

Two signals cause ADH to be released, these are:

1. Osmoreceptors: increased extracellular fluid osmolarity
2. Baroreceptors: low blood volume/pressure

 When neural signals cause an action potential to propagate down the long axis of the PP depolarization causes the influx of Ca2+ ions. This causes neurosecretory granules to fuse with the cell membrane causing their contents to be released into the general circulation. At plamsa pH levels, neurophysin and the hormone are unbound. The hormones then travel to their target cells where they have a variety of physiological effects.

Functions: Oxytocin functions in the milk ejection reflex and parturition. It causes contraction of the myoepithelial cells surrounding the alveoli and walls of the excretory ducts of the mammary gland. This results in the ejection of milk. It also causes an increase in the frequency and strength of uterine contractions and is involved in a positive feedback loop which causes the foetus to be expelled during parturition. 

ADH functions in increasing the reabsorption of water at the distal neprhon of the kidney by increasing the insertion of aquaporin-2 channels into the apical membrane of principal cells (see this post).

Diabetes Insipidus (DI)

This is a form of diabetes associated with ADH (not insulin). Two types of DI can occur:

1. Central DI: Failure of ADH synthesis or secretion.
2. Nephrogenic DI: This is because of an inappropriate renal response to normal levels of ADH. 

In both cases renal water reabsorption is decreased and large volumes of dilute urine are passed. This presents as polyuria and polydipsia (PU/PD). 

That's it for this post, if you have any questions please feel free to ask :)