Comparison of the Long-Term Effects of Estrogen and Clomiphene Citrate on Pituitary and Uterine Function in Ovariectomized Rats

Abstract

The effects of estradiol-17Β (E₂) and clomiphene citrate (CC) on pituitary-uterine function in ovariectomized (OVX) rats were compared in two experiments. In experiment 1 CC completely blocked E₂ stimulation of uterine weight when administered concurrently for 10 and 30 days. In experiment 2, content of total (occupied and unoccupied) uterine nuclear estrogen receptors was increased by E₂, but not by CC, compared to OVX controls. Only a fraction of the nuclear receptors was occupied in E₂-treated rats, whereas all of these receptor sites were occupied in CC-treated rats. In addition, uterine cytoplasmic estrogen receptors were increased by E₂ and diminished by CC treatment. Both E₂ and CC were effective in preventing the postovariectomy rise in serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH), although LH was always inhibited to a greater extent than FSH. After 30 days of treatment, pituitary gonadotropins were also substantially reduced by E₂ and CC, suggesting that long-term treatment decreased both pituitary synthesis and release. An increase in pituitary weight observed in E₂-treated rats only was due largely to the stimulation of lactotropes, as serum prolactin was increased. In summary, although CC and E₂ similarly depressed pituitary gonadotropin secretion, they exhibited marked differences in the stimulation and occupancy of uterine estrogen receptors and the stimulation of pituitary prolactin secretion.

Oestradiol stimulates prolactin secretion in women through oestrogen receptors

“…However, a study in ovariectomized rats treated with clomiphene for 30 days showed no changes in serum PRL levels. 15 Similarly, when clomiphene was given to subfertile men at the dose of 50 mg/day for 3 months, basal PRL levels remained unchanged. 19 In the present study, serum PRL levels did not change even after the addition of E2 to the clomiphene or raloxifene regimen.…”

“…Regarding clomiphene, the literature lacks data on the effect of this compound on PRL secretion in postmenopausal women. However, a study in ovariectomized rats treated with clomiphene for 30 days showed no changes in serum PRL levels 15 . Similarly, when clomiphene was given to subfertile men at the dose of 50 mg/day for 3 months, basal PRL levels remained unchanged 19 …”

“…Raloxifene is a new anti‐oestrogenic drug that shows actions that are different from those of clomiphene regarding the secretion of gonadotrophins with no oestrogenic activity in postmenopausal women 13 . Data on the effects of these agents on PRL secretion are scanty and mainly based on experiments in animals 14–16 . In women, information is limited to a suppressing effect of raloxifene on PRL levels at 3 and 6 months of treatment with this compound for the prevention of postmenopausal osteoporosis 17 .…”

“…13 Data on the effects of these agents on PRL secretion are scanty and mainly based on experiments in animals. [14][15][16] In women, information is limited to a suppressing effect of raloxifene on PRL levels at 3 and 6 months of treatment with this compound for the prevention of postmenopausal osteoporosis. 17 However, the effect of clomiphene or raloxifene on GnRH-induced PRL secretion has not been investigated.…”