sleep (Arendt 2003; Cajochen et al. 2003); regulation of reproductive physiology in seasonal breeders (Aleandri et al. 1997; Reiter 1998; Stehle et al. 2003); effects on calcium and phosphorus metabolism, parathyroid activity, bone growth, and development of postmenopausal osteoporosis (Chen et al. 1990, 1991; Sandyk et al. 1992; Shoumura et al. 1992; el-Hajj Fuleihan et al. 1997; Roth et al. 1999; Cardinali et al. 2003; Goodman 2003); oncostatic or anticarcinogenic effects (Cohen et al. 1978; García-Patterson et al. 1996; Panzer 1997; Anisimov 2003); antioxidant actions (Srinivasan 2002; Reiter et al. 2003b); and effects on the central nervous system, psychiatric disease, and sudden infant death syndrome (García-Patterson et al. 1996; Reiter 1998; Delagrange et al. 2003). Panzer (1997) suggested that the simultaneous decrease in melatonin concentrations and the exponential increase in bone growth during puberty could be a factor in the typical age distribution of osteosarcoma.

Pineal Gland Calcification

The pineal gland is a calcifying tissue; in humans, calcified concretions can be found at any age, although the likelihood increases with age (Vígh et al. 1998; Akano and Bickler 2003) and may be associated with menopause (Sandyk et al. 1992). The occurrence of pineal calcifications varies among different populations and nations (Vígh et al. 1998), possibly in association with the degree of industrialization (Akano and Bickler 2003), rates of breast cancer (Cohen et al. 1978), and high circannual light intensity near the equator (Vígh et al. 1998). Osteoporosis might be associated with fewer concretions (Vígh et al. 1998).

Melatonin secretion is well correlated with the amount of uncalcified pineal tissue (Kunz et al. 1999) but not with the size of pineal calcification (Vígh et al. 1998; Kunz et al. 1999). An increase in calcification of the pineal gland in humans probably represents a decrease in the number of functioning pinealocytes and a corresponding decrease in the individual’s ability to produce melatonin (Kunz et al. 1999). The degree of calcification, relative to the size of an individual’s pineal gland, has been suggested as a marker of the individual’s decreased capability to produce melatonin (Kunz et al. 1999).

As with other calcifying tissues, the pineal gland can accumulate fluoride (Luke 1997, 2001). Fluoride has been shown to be present in the pineal glands of older people (14-875 mg of fluoride per kg of gland in persons aged 72-100 years), with the fluoride concentrations being positively related to the calcium concentrations in the pineal gland, but not to the bone fluoride, suggesting that pineal fluoride is not necessarily a function of cumulative fluoride exposure of the individual (Luke 1997, 2001). Fluoride has not been measured in the pineal glands of children or young adults, nor



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