MRC National Institute for Medical Research, London
Science for Health
Paul Le Tissier group
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Control of prolactin and growth hormone cell differentiation and function
The hormones prolactin (principally involved in pregnancy and production of milk) and growth hormone (required for normal growth and metabolism) are secreted from specialised cells of the anterior pituitary gland, located just under the brain. The function, development and regulation of prolactin and growth hormone cells are closely related and we are studying the control of their function and interrelationship using transgenic mice. These studies also reveal the effects of alterations of prolactin and growth hormone cells on other pituitary hormones regulating stress, reproduction and metabolism. Knowing how these cell populations are controlled normally is important for understanding how hormone deficiencies or pituitary tumours occur when this regulation fails.
We have generated transgenic mice with different proportions of growth hormone cell ablation. The degree of ablation correlates with effects on the other pituitary hormones, with prolactin the most affected. Loss of growth hormone cells also leads to a disruption of the normal organisation of cells within the pituitary, which may have consequences for the secretory response to releasing factors.
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Real-time monitoring of inhibition of prolactin secretion from a pituitary slice in response to different concentrations of dopamine.
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Growth hormone cells are normally organised in a network in the pituitary gland, shown by expression of green fluorescent protein (left panel). Ablation of growth hormone cells disrupts this organisation but cells still form clusters (middle panel), whereas transgenic mice with a loss of growth hormone cell proliferation fail to form clusters, despite a similar cell density (right panel).
Selected publications
- Lafont, C; Desarménien, MG; Cassou, M; Molino, F; Lecoq, J; Hodson, D; Lacampagne, A; Mennessier, G; El Yandouzi, T; Carmignac, D; Fontanaud, P; Christian, H; Coutry, N; Fernandez-Fuente, M; Charpak, S; Le Tissier, P; Robinson, ICAF and Mollard, P (2010)
Cellular in vivo imaging reveals coordinated regulation of pituitary microcirculation and GH cell network function.
Proceedings of the National Academy of Sciences of the United States of America 107, 4465-4470 PubMed abstract - Waite, E; Lafont, C; Carmignac, D; Chauvet, N; Coutry, N; Christian, H; Robinson, I; Mollard, P and Le Tissier, P (2010)
Different degrees of somatotroph ablation compromise pituitary growth hormone cell network structure and other pituitary endocrine cell types.
Endocrinology 151, 234-243 PubMed abstract - Le Tissier, PR; Carmignac, DF; Lilley, S; Sesay, AK; Phelps, CJ; Houston, P; Mathers, K; Magoulas, C; Ogden, D and Robinson, ICAF (2005)
Hypothalamic growth-hormone-releasing-hormone (GHRH) deficiency: targeted ablation of GHRH neurons in mice using a viral ion channel transgene.
Molecular Endocrinology 19, 1251-1262 PubMed abstract
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