Thursday 2 April 2015

Main Squeeze

I mentioned the posterior pituitary in passing almost exactly two years ago, when I was on a reflective high about the fun I was having at work. The pituitary is Mission Control for the endocrine system producing at least a dozen hormones from its location right in the middle of the head. The gland, about the size of a chick-pea, aka the hypophysis, is attached by a wee stalk to the hypothalamus which is below the thalamus. It's like the hanging gardens in there. The pituitary is actually two glands, which happen to be stuck together.  The anterior pituitary is a bear-pit of activity producing a clatter of hormones, many of them tropic hormones: hormones the control other hormones. That's a very common way of giving micro-switch control to the endocrine system to maintain levels close to a homeostatic set point rather than lurching from feast to famine. Several diseases are caused when the delicate balance breaks down and the levels of a hormone fluctuates wildly up and down. Medication and medical intervention is never as good as the natural system cobbled together from recycled parts by evolution.

Eugene Geiling, whom we've met before as a mentor to Frances "Thalidomide" Kelsey, was a pioneer in the early days of molecular endocrinology. To get enough material to charactertise the tiny, hyper-dilute, peptide hormones which he discovered he needed a helluva lot of pituitary.  Rather than working through hundreds of lab rats, he had the bright idea of using a whale as a one-stop shop and went at a whale's head with an axe and a saw.  It was a change from the probes and scalpels he was used to handling, but he was able to show that substances produced in the posterior lobe - ultimately named as oxytocin and vasopressin - had particular, peculiar and pervasive effects on other parts of the body.  Not on the whale's body, it was dead to all effects, but on yours and mine.

As far as we know the posterior pituitary makes only two hormones - oxytocin and vasopressin - and their existence is rather good evidence of evolution. You can see from the picture left that the business end of these two hormones, a 9 amino acid small peptide, are carved from two much larger proteins.  Each letter in the alignment represents one of the 20 amino acids that are used by the genetic code to make all the proteins we use. The stars under the alignment indicate that even after many years of independent evolution the two genes are strikingly similar, notably the two short 'mature' peptides which do the heavy lifting are 7/9th identical - the two changes have completely changed the function of the two hormones.  Or not.  The picture below shows that the genes encoding these proteins are next-door neighbours in the human genome. Once upon a time in this location there was only one gene: millions of years ago there was stutter in the replication process for chromosome 20 and this section was duplicated.
But maybe the evolution of these two hormones was not now for something completely different. It turns out that vasopressin is essential for managing blood-pressure: the name on its tin says that it raises pressure in the vascular (blood) system by squeezing the smooth muscles on arteries. Remarkably, this hormone has another completely different function and an alternative name - anti-diuretic hormone ADH - which also states its function: ADH squeezes the kidney tubules and stops you peeing; retaining water in this way also cranks up the blood-pressure.  That's pretty neat in my book - a double whammy providing redundancy in controlling this vital equilibrium.  If your kidneys are shot and ADH has nothing to operate on, vasopressin can still control blood-pressure by its action on the smooth muscles.

Oxytocin is also amazingly versatile.  It gets its name from the Greek ὀξύς + τόκος [oxys-tokos] = sharp/quick birth.  Same root as oxygen which tends to generate acids (another meaning of sharp). If your pregnancy is more than a week over 9 months, you'll get an intravenous drip of oxytocin which will precipitate the birth process by inducing uterine contractions squeezes.  That's what oxytocin does naturally in the non-interventionist world of normal childbirth. A few hours later, the hormone starts another essential role about 50cm North, by squeezing the milk ducts as the let-down reflex in the breast to eject milk into the ravenous maw of the newborn child.  Just like vasopressin, same hormone, different, related function - we just haven't got round to giving it another name yet. If the mother and child don't set up an affiliative mutually-engaged relationship pretty damn quick, then all that squeezing in the uterus and mammary gland will come to nothing.  Amazingly, some parts of the brain evolved a sensitivity to oxytocin that causes a behavioural change to promote bonding. There is emerging evidence that it is associated with bonding not only between mother and child but by extension between mother and partner: which in some parts of the Anglophone world is called her Main Squeeze.  You couldn't make this up!

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