Investigation of the role of prolactin in the development and function of the lacrimal and harderian glands using genetically modified mice.
OBJECTIVE
To determine whether prolactin receptor is essential for normal development and function of the lacrimal gland and whether hyperprolactinemia can alter lacrimal development.


METHODS
Lacrimal gland morphology and function were examined in two genetic mouse models of prolactin action: a prolactin receptor knockout model that is devoid of prolactin action and a transgenic model of hyperprolactinemia.


RESULTS
Image analysis of lacrimal and Harderian gland sections was used to quantify glandular morphology. In females, lacrimal acinar area decreased by 30% and acinar cell density increased by 25% over control subjects in prolactin transgenic animals, but prolactin receptor knockout mice showed no changes. In males, transgenic animals showed no changes, but prolactin receptor knockout mice showed a 5% reduction in acinar area and an 11% increase in acinar cell density, which was lost after castration. The morphology of the Harderian glands underwent parallel changes but to a lesser degree. A complete loss of porphyrin accretions was seen in the Harderian glands of male and female knockout animals. No differences in tear protein levels were seen in knockout animals by two-dimensional gels. Enzyme-linked immunosorbent assay (ELISA) and Western blot analysis showed that the level of secretory component and IgA in knockout mouse tears remained unchanged. There was no change in the predisposition of the 129 mouse strain to conjunctivitis in the knockout animals.


CONCLUSIONS
Prolactin plays a small role in establishing the sexual dimorphism of male lacrimal glands. In females, hyperprolactinemia causes a hyperfemale morphology, suggesting a role in dry eye syndromes. Prolactin is required for porphyrin secretion by the Harderian gland but plays no essential role in the secretory immune function of the lacrimal gland.
McClellan
K A
KA
Department of Ophthalmology, University of Sydney, Sydney Eye Hospital, Australia.
Robertson
F G
FG
Kindblom
J
J
Wennbo
H
H
Törnell
J
J
Bouchard
B
B
Kelly
P A
PA
Ormandy
C J
CJ
D000818:Animals; D015153:Blotting, Western; D002452:Cell Count; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay; D005136:Eye Proteins / Q000378:metabolism; D005260:Female; D006243:Harderian Gland / Q000166:cytology* / Q000502:physiology*; D006966:Hyperprolactinemia / Q000235:genetics / Q000378:metabolism; D007765:Lacrimal Apparatus / Q000166:cytology* / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011388:Prolactin / Q000502:physiology*; D011981:Receptors, Prolactin / Q000235:genetics / Q000502:physiology; D012727:Sex Characteristics; D013666:Tears / Q000378:metabolism
D005136:Eye Proteins; D011981:Receptors, Prolactin; C042434:tear proteins; D011388:Prolactin