Cellular in vivo imaging reveals coordinated regulation of pituitary microcirculation and GH cell network function.
Growth hormone (GH) exerts its actions via coordinated pulsatile secretion from a GH cell network into the bloodstream. Practically nothing is known about how the network receives its inputs in vivo and releases hormones into pituitary capillaries to shape GH pulses. Here we have developed in vivo approaches to measure local blood flow, oxygen partial pressure, and cell activity at single-cell resolution in mouse pituitary glands in situ. When secretagogue (GHRH) distribution was modeled with fluorescent markers injected into either the bloodstream or the nearby intercapillary space, a restricted distribution gradient evolved within the pituitary parenchyma. Injection of GHRH led to stimulation of both GH cell network activities and GH secretion, which was temporally associated with increases in blood flow rates and oxygen supply by capillaries, as well as oxygen consumption. Moreover, we observed a time-limiting step for hormone output at the perivascular level; macromolecules injected into the extracellular parenchyma moved rapidly to the perivascular space, but were then cleared more slowly in a size-dependent manner into capillary blood. Our findings suggest that GH pulse generation is not simply a GH cell network response, but is shaped by a tissue microenvironment context involving a functional association between the GH cell network activity and fluid microcirculation.
Department of Endocrinology, Institute of Functional Genomics, Montpellier 34094, France.
Chrystel
C
Lafont
Michel G
MG
Desarménien
Mathieu
M
Cassou
François
F
Molino
Jérôme
J
Lecoq
David
D
Hodson
Alain
A
Lacampagne
Gérard
G
Mennessier
Taoufik
T
El Yandouzi
Danielle
D
Carmignac
Pierre
P
Fontanaud
Helen
H
Christian
Nathalie
N
Coutry
Marta
M
Fernandez-Fuente
Serge
S
Charpak
Paul
P
Le Tissier
Iain C A F
IC
Robinson
Patrice
P
Mollard
D000818:Animals; D013006:Growth Hormone / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008833:Microcirculation; D010902:Pituitary Gland / Q000098:blood supply* / Q000166:cytology / Q000378:metabolism
D013006:Growth Hormone