Investigation of the role of prolactin in the development and function of the lacrimal and Harderian glands using genetically modified mice

PURPOSE. TO determine whether prolactin receptor is essential for normal de velopment and function of the lacrimal gland and whether hyperprolactinemia can alter lacrimal development. METHODS. Lacrimal gland morphology and function were examined in two geneti c mouse models of prolactin action: a prolactin receptor knockout model tha t is devoid of prolactin action and a transgenic model of hyperprolactinemi a. RESULTS. Image analysis of lacrimal and Harderian gland sections was used t o quantify glandular morphology. In females, lacrimal acinar area decreased by 30% and acinar cell density increased by 25% over control subjects in p rolactin transgenic animals, but prolactin receptor knockout mice showed no changes, in males, transgenic animals showed no changes, but prolactin rec eptor knockout mice showed a 5% reduction in acinar area and an 11% increas e in acinar cell density, which was lost after castration. The morphology o f 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 wer e seen in knockout animals by two-dimensional gels. Enzyme-linked immunosor bent assay (ELISA) and Western blot analysis showed that the level of secre tory component and IgA in knockout mouse tears remained unchanged. There wa s 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 dimorp hism of male Lacrimal glands. In females, hyperprolactinemia causes a hyper female morphology, suggesting a role in dry eye syndromes. Prolactin is req uired for porphyrin secretion by the Harderian gland but plays no essential role in the secretory immune function of the lacrimal gland.