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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of pineal research 1 (1984), S. 0 
    ISSN: 1600-079X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The purpose of this study was to define the peripubertal changes in prolactin (PRL) synthesis in blind-anosmic female rats. To do this prepubertal female rats were either rendered blind-anosmic (BA) or blind-anosmic-pinealectomized (BAP) or left intact (INT). Half the animals were killed after 1 wk (before puberty) while the remaining animals were terminated after 4 wk (after puberty). Pituitary PRL synthesis was measured by the in vitro incorporation of 3H-leucine into PRL. Anterior pituitary weight and DNA content did not differ between BA, BAP, and INT animals 1 wk after treatment. There was a 65% increase in weight and a 55% increase in DNA content in INT pituitaries between I and 4 wk. White these increases were also present in BAP rats, they were almost entirely prevented in BA animals. PRL synthesis followed a similar pattern with a 78% increase in synthesis in INT groups between 1 and 4 wk which was, once again, almost entirely absent in BA rats. Pinealectomy prevented this effect. Blinding and anosmia in postpubertal animals produced only a minor decrease in PRL synthesis and pituitary weight and no decrease in pituitary cell number. From these data we conclude that the pineal can inhibit the normal proliferation of PRL cells that occurs during puberty in blind-anosmic female rats.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of pineal research 10 (1991), S. 0 
    ISSN: 1600-079X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Cos S, Blask DE, Lemus-Wilson A, Hill AB. Effects of melatonin on the cell cycle kinetics and “estrogen-rescue of MCF-7 human breast cancer cells in culture. J Pineal Res 1991:10:3642.〈section xml:id="abs1-1"〉〈title type="main"〉Abstract:Melatonin has been shown to have a direct inhibitory action on the proliferation of estrogen-responsive MCF-7 human breast cancer cells in culture. In the present study, we examined by flow cytometry whether this inhibitory effect might be exerted on the G1 phase of the cell cycle, thus causing a transition delay into the S phase. In order to further verify this hypothesis we tested the ability of estradiol to “rescue” MCF-7 cells from melatonin inhibition, and the potential of this indoleamine to block the ability of estradiol to rescue the cells from tamoxifen inhibition. Following five days of incubation, melatonin (10-9M) increased the fraction of cells in G1 of the cell cycle while simultaneously causing a 50% reduction in the proportion of cells in S phase. The antiproliferative effect of melatonin (11-5M) was prevented by the simultaneous treatment of the cells with estradiol (10-8M) in clonogenic soft agar culture, or reversed by the addition of estradiol to cells previously incubated with and inhibited by melatonin (10-9M) in monolayer culture. Additionally, melatonin blocked the estrogen-rescue of tamoxifen-inhibited cells in both types of culture systems. These results support the hypothesis that the antiproliferative effect of melatonin, like tamoxifen, is cell cycle specific by causing a G1-S transition delay. These results also indicate an important interaction of melatonin with estrogen-mediated mechanisms of MCF-7 cell proliferation.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of pineal research 17 (1994), S. 0 
    ISSN: 1600-079X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Cos S, Blask DE. Melatonin modulates growth factor activity in MCF-7 human breast cancer cells. J. Pineal Res. 1994: 17: 25–32.〈section xml:id="abs1-1"〉〈title type="main"〉AbstractMelatonin has been shown to have direct oncostatic actions on estrogen-responsive, MCF-7 human breast cancer cells in culture. In the present study, we examined whether these inhibitory actions on cell growth may be mediated through actions on bioassayable growth factor activity. In order to test this hypothesis, we estimated the growth factor activity of conditioned medium (CM) from estradiol (E2), or melatonin-treated cells, in the presence or absence of melatonin on MCF-7 cell growth. We also determined whether melatonin inhibits the action of epidermal growth factor (EGF) action in the absence of E2. The addition of melatonin (10-9 M) to the cultures of MCF-7 cells with CM from E2 (10-8 M)-treated cells significantly inhibited the growth stimulatory activity of CM, suggesting that melatonin inhibited cell proliferation by blocking the action of E2-induced autocrine growth stimulatory factors. Conditioned medium from melatonin-treated cells significantly inhibited cell proliferation, while an additional supply of melatonin to these cultures had an even greater inhibitory effect. Melatonin was also active in the complete absence of serum as long as cell growth was stimulated by EGF, an E2-inducible growth factor. The inhibitory effect of melatonin increased as the dose of EGF increased. This non-antiestrogenic inhibitory effect of melatonin was reversed by E2, but not by EGF itself, suggesting that melatonin requires accessible estrogen receptor sites for its inhibitory activity on the growth stimulating action of EGF. Taken together, these findings suggest that melatonin may inhibit the action and/or release of growth stimulatory factors as well as stimulate the release of growth inhibitory factors in culture. Furthermore, these findings indicate an important interaction of melatonin with E2-inducible autocrine growth factors such as EGF in the inhibition of MCF-7 cell growth.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1600-079X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The combination of pituitary grafts and daily injections of gonadotrophin-releasing hormone (GnRH) completely prevents gonadal atropy in blind (BL) and melatonin (Mel)-treated male hamsters. In order to avoid potential problems associated with the use of pituitary grafts and further define the interactions between prolactin (PRL) and GnRH in preventing reproductive regression, we injected various doses of each hormone either alone or in combination into BL or Mel-treated male hamsters. In another experiment, BL hamsters received either weekly beeswax implants of estradiol benzoate (EB) (1 mg) alone or EB implants in combination with daily injections of GnRH (2 μg). In each experiment the hamsters were BL and/or treated with hormones for 10 wk. Either GnRH (8 fig) or PRL (5 μg) per d partially prevented gonadal atrophy in BL hamsters. However, increasing doses of GnRH plus PRL wre more effective than either hormone alone in preventing gonadal atrophy. The combined effect of these hormones was greater than the algebraic sum of their individual effects. Injections of either GnRH or PRL alone resulted in a significant maintenance of gonadal and accessory organ size in Mel-treated animals. The combination of GnRH and PRL resulted in virtually complete maintenance of testicular weight while the accessory sex organs remained atrophic. The combined effect of these hormones was equivalent to the algebraic sum of their individual effects. The treatment of BL animals with EB implants with or without GnRH did not prevent reproductive regression in spite of elevated serum PRL levels. In conclusion, the effects of GnRH and PRL were synergistic in BL hamsters and additive in Mel-treated animals. The data suggest that there is a differential responsiveness of BL v. Mel-treated hamsters to the individual as well as the combined actions of GnRH and PRL.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of pineal research 7 (1989), S. 0 
    ISSN: 1600-079X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The purpose of this study was to determine and compare the effects of chronic melatonin treatment in vivo on several aspects of prolactin (PRL) cell activity (PRL synthesis, storage, and release) in vitro in male and female Syrian hamsters. Adult male and female hamsters were maintained on long photoperiod and treated with daily late afternoon injections of melatonin (25 μg) or vehicle for 11 weeks. Melatonin treatment resulted in an 85% and 65% decrease in serum PRL levels in male and female hamsters, respectively. There was a similar 79% and 64% decrease in PRL release in vitro from pituitaries of male and female hamsters, respectively, treated with melatonin in vivo. Total stored PRL was 75% lower in male hamsters and 62% lower in female hamsters receiving melatonin. The synthesis of PRL by pituitaries from melatonin-treated male hamsters was reduced by 65%, whereas in melatonin-treated females it was decreased by 58%. Both nanomolar and micromolar doses of melatonin in vitro caused a modest but significant decrease (14–19%) in the amount of PRL stored in and released from normal male pituitaries without affecting synthesis. The inhibitory effects of melatonin on PRL cell function appear to be more pronounced in male than in female hamsters suggesting a sexually dimorphic response to this pineal hormone. While melatonin's PRL-inhibitory effects appear to be exerted primarily via indirect neuroendocrine mechanisms, a secondary component of its overall regulation of PRL processing may involve direct pituitary mechanisms as well.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of pineal research 3 (1986), S. 0 
    ISSN: 1600-079X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Removal of the pineal gland produces stereotyped tonic convulsions in parathyroidectomized rats. Inasmuch as central levels of norepinephrine (NE) are decreased in these animals, the purpose of this study was to investigate the effects of alterations in central catecholamine function on convulsions produced by pinealectomy in parathyroidectomized rats. The treatment of rats with α-methyl-p-tyrosine or FLA-63 produced large reductions in forebrain levels of both NE and dopamine or NE alone, respectively, which were not associated with facilitation of convulsions. However, the incidence of convulsions was increased by FLA-63 in rats pretreated with the catecholamine precursor L-dihydroxyphenylalanine. Reserpine, a monoamine depleter, had no effect on either the incidence or severity of convulsions. An acute injection of desipramine, an inhibitor of the reuptake of NE, however, significantly lowered the incidence of convulsions. Timolol, a β-adrenergic receptor antagonist, reduced, in a dose-dependent manner, the average latency to onset of convulsions and increased the average number of convulsions each rat experienced. Clonidine, an α2-adrenergic agonist, did not significantly alter convulsions. Thus presynaptic mechanisms such as synthesis and storage of both NE and DA appear to have little, if any, effect on pinealectomy-induced convulsions, whereas enhancing synaptic levels of NE by blocking its reuptake into adrenergic axons had an anticonvulsant effect. Further evidence suggesting a role for NE in modulating these convulsions is provided by the proconvulsant effect of blocking central β-adrenergic receptors.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-1335
    Keywords: Pineal ; Melatonin ; Breast cancer ; Hormones ; N-Nitroso-N-methylurea
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary TheN-methyl-N-nitrosurea (NMU) model of hormone-responsive rat mammary carcinogenesis was used to address the hypothesis that melatonin (Mel), the principle hormone of the pineal gland, inhibits tumorigenesis by acting as an anti-promoting rather than an anti-initiating agent. Daily late-afternoon injections of Mel (500 μg/day), restricted to the initiation phase of NMU mammary tumorigenesis, were ineffective in altering tumor growth over a 20-week period. When Mel treatment was delayed for 4 weeks after NMU and then continued through the remainder of the promotion phase, only tumor number was significantly lower than in controls. However, when Mel injections encompassed the entire promotion phase, both tumor incidence and number were significantly lower than in the controls. Although elimination of the endogenous Mel signal via pinealectomy promoted tumor growth, the effect was not statistically significant. Serum levels of estradiol and tumor estrogen receptor content were unaltered by either Mel or pinealectomy. While Mel treatment failed to affect circulating prolactin levels, pinealectomy caused a two-fold increase in serum prolactin. The estradiol-stimulated recrudescence of tumors following ovariectomy was completely blocked by either 20, 100 or 500 μg Mel/day or tamoxifen (20 μg/day). Thus, Mel appears to be an antipromoting hormone that may antagonize the tumor-promoting actions of estradiol in this model of mammary tumorigenesis.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0878
    Keywords: Pineal gland ; Prolactin ; Mammotroph ; Blind-anosmic ; Pituitary
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The effects of the pineal gland on the light microscopic-immunocytochemical and ultrastructural appearance of pituitary mammotrophs were studied in female rats eight weeks after prepubertal blinding and olfactory bulbectomy. Blinding and anosmia resulted in a marked decrease in the size of the pars distalis concomitant with a reduction in the apparent number and size of PRL cells as compared with intact animals. Ultrastructurally, these cells appeared much less active than those of intact rats. The small and angular-shaped mammotrophs of blind-anosmic rats characteristically exhibited scant arrays of rough endoplasmic reticulum, small Golgi complexes with few immature secretory granules, few mature secretory granules and rare exocytosis patterns. Pinealectomy tended to reverse the effects of blinding and anosmia on pars distalis size and PRL cell size, apparent number and ultrastructure. In fact, the mammotrophs of blind-anosmic-pinealectomized rats were quite similar in ultrastructural appearance to those of intact rats. From these data we conclude that the pineal causes mammotroph hypotrophy and hypoplasia in blind-anosmic female rats.
    Type of Medium: Electronic Resource
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