The human pineal gland and melatonin-regulating factors: Morphometry, cellularity and c-kit-positive cells

Abstract

Introduction: The human pineal gland exhibits endocrine activity derived from the diencephalon and is divided into lobules by pial connective tissue. Its morphometry and cellularity might be set up during the early years of development (by cell proliferation and apoptosis). The presence of glia-derived astrocytes has been described in the pineal gland stroma. However, c-kit (CD-117) positive cells have not been described yet in this organ. Aims: In this study, the morphometry, cellularity and presence of c-kit + cells in the human pineal gland (which expresses the membrane receptor with protein kinase III activity) will be assayed. Material and methods: Human pineal glands distributed in 4 groups according to age: a) group 1, 1 to 6 years, n = 6; b) group 2, 12 to 17 years, n = 3; c) group 3, 20 to 30 years, n = 3; and d) group 4, 35 years old, n = 3; were fixed in pH 7.2 formol during 48 h. They were included in paraffin for histological examination, and a series of 5-µm sections were obtained for hematoxylin-eosin staining. Sections were analysed for histological morphometry (lobule diameter and nuclear area) and quantification of proliferative and apoptotic cell number (cell number/0.17 mm2) by specific immunohistochemistry (IHC) for identification of Ki-67, Apaf-1 (Vector Co.) and c-Kit testing (DAKO A4502). Results and discussion: Here we demonstrated changes in morphometry and cellularity of the human pineal gland according to age, with an increase in cell size until the young adulthood and in cell proliferation during adolescence period, in addition to the high rate of apoptotic index in the first years of life and its progressive reduction during the following years. Besides, it was possible to demonstrate the presence of interstitial Cajal cells expressing the receptor c-kit in groups 2, 3 and 4 only, located in the gland interstice. Apparently, the human pineal gland finishes its development during puberty when the c-kit positive cells appear. These cells may act as membrane depolarization foci (pacemaker), thus resulting in melatonin release. Simultaneously degenerative signs appeared in the group of oldest age, as demonstrated by the presence of calcified structures.