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Instituto Latinoamericano de Fisiología de la Reproducción (I.L.A.F.I.R.), C.C. 10- San Miguel, P.B.A., Argentina
(Received 6 May 1975)
Previous investigations have indicated that the rat pineal gland, besides constituting a neuroendocrine transducer able to convert neural inputs originating in retinal photoreceptors and reaching the pinealocytes through their sympathetic nerves (Wurtman & Antón-Tay, 1969), has the capacity to respond to a variety of hormone signals in the circulation which include gonadal steroids (see below) and catecholamines (Lynch, Eng & Wurtman, 1973). Protein receptors for sex hormones are present within pineal cells and are controlled via a β-adrenergic receptor by the noradrenaline released from pineal nerve-endings (Cardinali, Nagle & Rosner, 1975). Treatment with oestradiol (Cardinali, Nagle & Rosner, 1974) or testosterone (Nagle, Cardinali & Rosner, 1974, 1975) enhances pineal melatonin and protein synthesis, a finding which suggests that a negative feedback operates between the gonads and the pineal gland of the rat.
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Several authors have proposed histamine as the mediator of oestrogen action (Holden, 1939; Spaziani & Szego, 1958), and the uterine release of histamine during early pregnancy has also been considered an oestrogenic effect (Shelesnyak, 1960), though later work proved this to be unlikely (Marcus & Shelesnyak, 1967). We have studied the influence of histamine on the uptake of oestradiol-17β by its target organs.
Adult female Wistar rats, ovariectomized 2 weeks previously, were injected s.c. with 5·76 × 106 d.p.m. of [6,7-3H]oestradiol-17β in 0·5 ml 0·9% NaCl solution. Oestradiol-17β (Nuclear Chicago Inc., sp. act. 40 Ci/mm) was previously purified by paper chromatography in benzene—formamide (Neher, 1964). Immediately after injection of the steroid, the experimental group received 50 mg histamine dihydrochloride s.c. in 0·5 ml 0·9% NaCl solution while control animals received only the vehicle.
The animals were killed 75 min later by cervical dislocation, and radioactivity was
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After decades of contradictory results it has become apparent that the mammalian pineal exerts an inhibitory influence on several neuroendocrine functions, namely the hypophysial-gonadal system, the adrenal cortex and the thyroid gland (Wurtman, Axelrod & Kelly, 1968). Among pineal secretory products the best characterized is melatonin (5-methoxy-N-acetyltryptamine), which reverses many of the endocrine changes that follow pinealectomy and mimics the effect of injecting pineal extracts into experimental animals. In the last 15 years considerable information has been accumulated on the mechanisms involved in the regulation of pineal melatonin synthesis; very little is known, however, about the biochemical processes evoked by melatonin in its target organs. Exogenous melatonin has been shown to become concentrated within the hypothalamus (Antón-Tay & Wurtman, 1969; Cardinali, Hyyppä & Wurtman, 1973). Implants of melatonin in the hypothalamus decrease pituitary gonadotrophin levels (Fraschini, 1969); moreover, melatonin perfusions of the third ventricle decrease plasma levels of
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SUMMARY
The effect of doses of oestradiol ranging from 0·0125 to 1·6 μg on the uterine weight of the spayed rat was studied 24 h after a single s.c. injection of the hormone. The lowest dose inducing a significant increase in uterine weight was 0·32 μg. When histamine dihydrochloride (50 mg) was simultaneously injected with the hormone, the effect of small doses of oestradiol (0·0125–0·2 μg) was significantly increased.
When oestradiol and histamine were administered for 3 successive days, the uterine weight of animals receiving 0·0125 μg oestradiol, if compared with untreated controls, was increased only in the histamine-treated group. When 0·05 μg oestradiol was administered, histamine did not modify the increase already produced by the hormone.
Spermidine and burimamide, two substances structurally related to histamine, increased [3H]oestradiol uptake by the spayed rat uterus. The latter (an antihistamine drug acting on H2-receptors) as well as pyrathiazine (a histamine releaser having antihistamine properties) decreased the effect of histamine on oestradiol uptake whereas diphenhydramine (an antihistamine drug blocking H1-receptors) did not modify it. Pyrathiazine was itself able to diminish oestradiol uptake.
