MRC National Institute for Medical Research, London
Science for Health
The organization of growth hormone cells affects secretory output
24 November 2010
NIMR scientists, with their collaborators in Montpellier, have shown that the organization of cells in the pituitary gland contributes to the sexually dimorphic output of growth hormone. The research is published in Proceedings of the National Academy of Sciences, USA.
In most species, males and females display a marked divergence in body size, with increased growth rate and body mass being a predominantly masculine trait, reflecting sex-specific differences in the growth hormone (GH) system. The secretion of GH is controlled by GH-releasing hormone (GHRH) and somatostatin (SRIF) and there is good evidence for sex-specific imprinting due to gonadal steroid exposure early in life with ongoing effects in puberty. This has led to the conclusion that the sexually dimorphic control of GH patterns reflects sex differences in GHRH and somatostatin inputs to the pituitary gland.
Previous studies by Iain Robinson with Patrice Mollard’s group in Montpellier showed that GH cells are arranged in functionally organized networks, with distinct differences between males and females, raising the possibility that the responses of the network are different.
To explore whether male and female pituitary glands would show different responses to the same stimulus in the absence of any hypothalamic influence, Paul Le Tissier (pictured) from NIMR’s Division of Molecular Neuroendocrinology, and his collaborators from the University of Montpellier, monitored the calcium responses to an identical GHRH stimulus in populations of individual identified GH cells in slices taken from male and female transgenic GH-eGFP mouse pituitary glands.
They found that the GH cell network responses are sexually dimorphic, with a more coordinated response from a higher proportion of cells in males than in females, correlated with a higher GH release from male slices. The ability to correlate calcium responses with hormone output required a system developed at NIMR by Zhenhe He, which allows sensitive real-time monitoring of secretion. The response was not due to a permanent difference in the network architecture between male and female mice, since the sex difference in the proportions of GH cells responding to GHRH could be manipulated by postpubertal gonadectomy and hormone replacement, suggesting that the network responses are dynamically regulated in adulthood by gonadal steroids. Thus, the pituitary gland contributes to the sexually dimorphic patterns of GH secretion that play an important role in differences in growth and metabolism between the sexes.
The pituitary gland has been described as simply being a 'slave' to the 'master' hypothalamus but this shows that there is a much more complex relationship. This study shows for the first time that organisation of growth hormone cells is important in interpreting hypothalamic stimuli- an efficient way to ensure that the correct proportion of a population of cells respond to a stimulus is to have them communicating with each other, being organised makes this communication rapid.
Paul Le Tissier
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Monitoring of calcium responses to GHRH (10 nM) in GH-GFP cells in male (A) and female (B) pituitary slices loaded with the fluorescent calcium dye fura-2.
Original Article
The pituitary GH network responses are sexually dimorphic and regulated by gonadal steroids in adulthood.
Claudia Sanchez-Cardenas, Pierre Fontanaud, Zhenhe He, Chrystel Lafont, Anne-Cécile Meunier, Marie Schaeffer, Danielle Carmignac, François Molino, Nathalie Coutry, Xavier Bonnefont, Laurie-Anne Gouty-Colomer, Elodie Gavois, David J. Hodson, Paul Le Tissier, Iain C.A.F. Robinson, and Patrice Mollard.
Proceedings of the National Academy of Sciences, USA. Epub ahead of print. Publisher abstract
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