Page 331 - Vitamin D and Cancer

318 R. Vieth

Table 14.2 Similarities and Differences between the vitamin D system and the classic hormone
systems
Similarities to conventional Differences from the rest of the
hormones endocrine system
Signalling Endocrine 1,25(OH) D, Paracrine 1,25(OH) D, which is not
2
2
molecule which is released into normally released into circulation
circulation
Site of synthesis Endocrine gland for the vitamin Breast, prostate, many cell types
of signaling D system is the kidney
molecule
What is regulated Calcium absorption at the Cell cycle, proliferation, differentiation,
intestine many genes affected.
Feedback via Serum calcium and parathyroid Autocatabolism by CYP24
hormone, respectively (24-hydroxylase) induced by both
suppressing and stimulating the substrate 25(OH)D and the
secretion of 1,25(OH) D product, 1,25(OH) D.
2 2
Substrate (for hormones in general, Supply of vitamin D and 25(OH)D
availability substrate supply is not depend on UV light or food sources
rate limiting in the context that were once in UV light, and
of ability to produce a can range from deficiency to over
hormone) 200 nmol/L (80 ng/mL) without
supplements
Enzyme kinetics (for hormones in general, For CYP27B1 and CYP24, substrate
substrate supply is abundant concentrations are below the Km
and not rate limiting) of the enzyme. Hence the enzyme
activity is in a first-order relationship
with the substrates, 25(OH)D and
1,25(OH) D
2
Effect of season (for hormones in general, For most who live at temperate latitudes,
there is no seasonality in there is seasonality in substrate
substrate supply) supply to produce 1,25(OH) D
2

produces an increase in the rate of catabolism, by inducing 1,25(OH) D-24-
2
hydroxylase (CYP24). Tissue levels of both 1-hydroxylase [CYP27B1] and 24-
hydroxylase need to be balanced according to the prevailing supply of 25(OH)D. The
inverse relationship between these enzymes has been shown in vivo in rats [34].

14.2.1 Vitamin D Metabolism and Points of Regulation

The metabolism of vitamin D behaves in a manner consistent with the model
illustrated in Fig. 14.1, in which a molecule of vitamin D can flow through a series
of virtual compartments as represented for each metabolite. Flow is regulated at sev-
eral steps in the system. At the level of 25-hydroxylase in the liver, metabolism of the
vitamin D substrate is relatively automatic and unregulated. Passage of 25(OH)D at
the kidney into the hormone, 1,25(OH) D, is regulated tightly, depending on the need
2
for calcium. At peripheral tissues where its role in the prevention of cancer becomes