Effect of 1,25-dihydroxyvitamin D3 on the female reproductive system in rats.
Parenteral application of the active metabolite of vitamin D3, 1,25-dihydroxyvitamin D3, has been anticipated to have remarkable efficacy in secondary hyperparathyroidism. However, in a reproduction seg. I study in rats, poor reproductive performance was reflected in a decrease in the number of matings, implantations and live births. These changes were though reversible after treatment with the compound was discontinued. In order to clarify the mechanism of these reversible toxicities, the following were examined in female rats treated with the D3 metabolite: 1. effect on the estrous cycle (no treatment for 2 weeks, treatment for 3 weeks and recovery for 2 weeks), and 2. effect on the maintenance of pregnancy (treatment for 2 weeks before mating and during the gestation period). In both groups, the levels of calcium, calcitonin, PTH and progesterone in serum were measured, and histopathological examination of the thyroid, parathyroid, ovary and uterus was carried out. The following results were observed: 1) disturbance of the estrous cycle, 2) hypofunctional changes in the corpus luteum in the ovary, and the epithelium, endometrium and uterine gland in the uterus with a decrease in the serum progesterone level and 3) hypercalcemia with a decrease in calcitonin or PTH levels in serum with morphological changes including atrophy and cyst-formation in the parathyroid. However, the above changes were reversible, and recovery was observed after administration of the compound was discontinued. These results indicate that the hypercalcemia caused by 1,25-dihydroxyvitamin D3 disrupts endocrinological homeostasis which in turn temporarily disrupts the female reproductive system. Furthermore, it was suggested that 1,25-dihydroxyvitamin D3 itself directly influences on endocrinological organs (hypothalamus, pituitary, parathyroid and thyroid) and reproductive organs (ovary and uterus).
Horii
I
I
Department of Toxicology and Pathology, Nippon Roche Research Center, Kamakura, Japan.
Takizawa
S
S
Fujii
T
T
D000818:Animals; D001284:Atrophy; D002116:Calcitonin / Q000097:blood; D002117:Calcitriol / Q000633:toxicity*; D004971:Estrus / Q000187:drug effects; D005260:Female; D005836:Genitalia, Female / Q000187:drug effects*; D006934:Hypercalcemia / Q000139:chemically induced; D010053:Ovary / Q000187:drug effects; D010280:Parathyroid Glands / Q000187:drug effects / Q000473:pathology; D010281:Parathyroid Hormone / Q000097:blood; D011247:Pregnancy; D011255:Pregnancy Maintenance / Q000187:drug effects; D011374:Progesterone / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects; D014599:Uterus / Q000187:drug effects
D010281:Parathyroid Hormone; D011374:Progesterone; D002116:Calcitonin; D002117:Calcitriol