Melanocyte‐stimulating Hormone: A Clinical and Laboratory Study

The Placenta is Simply a Neuroendocrine Parasite

“…The mammalian and human arena inevitably attracted my interest, and, working in collaboration, Sandy Scott and I discovered the C‐terminal fragment of adrenocorticotrophic hormone (ACTH) [corticotrophin‐like intermediate peptide (CLIP)] in the pars intermedia (2), which led to the concept of tissue‐specific processing of its precursor pro‐opiomelanocortin (POMC) in different parts of the pituitary gland (3). As the adult human pituitary does not contain pars intermedia tissue and thus does not process POMC to the level of the melanotrophins, a process that takes place in most other mammalian species that do have a distinct intermediate lobe, I was intrigued to come across a paper that suggested that melanotrophic activity (bioassayed in intact frogs) was elevated in the blood of pregnant women and reached very high concentrations in pre‐eclampsia (4). It was also during my PhD studies that I was to realise the importance of post‐translational modification and how it affects biological activity.…”

“…My early attempts at investigating placental melanotrophin started with experiments using the in vitro frog skin bioassay (developed during my PhD) in which I was unable to repeat McGuiness’ observations (4) of increased melanotrophic activity in extracts of blood taken from mothers suffering from pre‐eclampsia; I concluded that his results may have been attributable to factors in the blood samples that would stimulate the frog’s pituitary (he had used an in vivo intact frog bioassay system) to secrete its own melanotrophin. Using a sensitive in vitro pituitary cell bioassay system, I had also started investigating the hypothalamic factor(s) responsible for the release of opiomelanocortins and, with Glenda Gillies, found that vasopressin and the 41‐residue peptide corticotrophin‐releasing factor (CRF) synergised in their activity at the pituitary corticotroph (5).…”

Broad Spectrum of Leukoderma Acquisitum Centrifugum

“…The importance of melanocyte stimulating hormone (MSH) elaborated by the pituitary gland is now well known. Evidence has been presented that destruction of the pitui¬ tary gland is accompanied by diminution of serum levels of MSH and hypopigmentation of the skin 65. The possibility exists that the pitui¬ tary metastasis in our patient may have been responsible in some manner for the unusual peritumoral leukoderma which developed around the cutaneous métastases.Drs.…”

Is 'pre-eclampsia' simply a response to the side effects of a placental tachykinin?

“…However, the presence in blood of a CRF-binding protein (Behan et al 1989, Linton et al 1993) that was effective in neutralising the activity of the placental CRF suggested it did not contribute to the PIH. There was also a discrepancy in the levels of CRF observed (3-fold) and the 'MSH activity' (100-fold) seen by McGuinness (1963). These observations led us to continue our search for the identity of the 'PE neuropeptide'.…”

“…We believe that any factor capable of causing PE must be able to inflict its effects not only at the utero-placental boundary but also at peripheral sites if it is to cause the diversity of symptoms seen in different patients. McGuinness (1963) first presented evidence that the PE factor may be a neuropeptide. An intact frog (skin) bioassay was used to demonstrate that there were grossly increased concentrations of 'melanocyte-stimulating hormone (MSH) activity' in extracts of plasma taken from women suffering from PE.…”