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Biomedical subjects

M K Vaughan

Publications and source records attributed to M K Vaughan.

At least 127 records · Page 7Linked to original sources

Prevention by melatonin of short day induced atrophy of the reproductive systems of male and female hamsters.

Male and female hamsters were exposed to natural photoperiodic and temperature conditions beginning on November 13 and groups of hamsters were necropsied either on January 15 or on April 10. Throughout the study, half of the hamsters (control hamsters) received subcutaneous implants of beeswax (25 mg) every other week while the other half received beeswax pellets containing 1 mg melatonin. Control beeswax-treated males necropsied in January had atrophic testes and accessory sex organs while the uteri of the control females were infantile in appearance. Melatonin treatment prevented the atrophic responses of the testes and accessory sex organs in males and the uteri in females. Melatonin-treated hamsters killed in January also had higher plasma levels of immunoreactive LH while in females both pituitary and plasma levels of LH were elevated after melatonin treatment. By April 10, the testes and accessory organs of control males and the uteri of control females had regenerated to the adult condition and these organs were comparable in size to those in melatonin-treated hamsters. The pituitary glands of control males contained slightly more LH and much more FSH than the pituitaries of melatonin-treated males. Melatonin-treated females necropsied in April had pituitary and plasma levels of LH and FSH similar to those in beeswax-treated females killed at the same time. The data show that chronic melatonin treatment prevents atrophy of the reproductive organs of male and female hamsters which is associated with the shortened days of the winter.

Animals↗

Influence of melatonin, constant light, or blinding on reproductive system of gerbils (Meriones unguiculatus).

Male and female gerbils were implanted s.c. with a pellet containing 2 mg melatonin/23 mg beeswax every 2 weeks for a total of 3 implants. A significant depression of ovarian and uterine weight was noted in female gerbils receiving melatonin implants. In the melatonin-treated male gerbils, growth of the accessory organs was significantly inhibited although testis size was not depressed.

Animals↗

Age-related changes in the intact and sympathetically denervated gerbil pineal gland.

The pineal gland of four-month-old gerbils contains numerous calcareous deposits (corpora arenacea or concretions). Also, the tissue appears vacuolated due to the presence of a number of large rounded spaces. The deposits are usually associated with or lying within these "vacuoles". By eight months of age, the number of both the corpora arenacea and the "vacuoles" are increased over those present in the pineals of four-month-old gerbils. Bilateral superior cervical ganglionectomy at one month of age prevents the formation of both the concretions and "vacuoles". The cells in the sympathetically denervated pineal glands are smaller than those in pineal glands of animals that possess intact superior cervical ganglia.

Aging↗

Melatonin induction of testicular recrudescence in hamsters and its subsequent inhibitory action on the antigonadotrophic influence of darkness on the pituitary-gonadal axis.

Exposure of adult male hamsters to light-dark (LD) cycles of 0:24 (in hours) for 12 weeks induced atrophy of the testes and accessory sex organs and a drop in immunoreactive pituitary and plasma prolactin levels. The subsequent exposure of these hamsters to LD 14:10 cycles caused regeneration of the sexual organs and an increase in pituitary LH and prolactin levels. Likewise, the weekly treatment of dark-exposed hamsters with subcutaneous melatonin-beeswax pellets led to regeneration of the peripheral reproductive organs and an increase in pituitary LH and prolactin levels. After gonadal regeneration, complete darkness failed to induce atrophy of the reproductive system indicating that either long photoperiods or melatonin treatment cause the pituitary-gonadal axis to be refractory to the inhibitory influence of darkness.

Animals↗

Melatonin inhibition of reproduction in the male hamster: its dependency on time of day of administration and on an intact and sympathetically innervated pineal gland.

The daily s.c injection of 25 microgram melatonin (MEL) in oil into adult male hamsters at 7 p.m. (lights on 6 a.m. to 8 p.m.) for 50 days caused involution of the tests, coagulation of gland and seminal vesicles and depression in pituitary prolactin (Prl) levels. Similar injections of MEL given at 9 a.m. completely failed to cause regression of the sex organs or a depression in pituitary Prl levels. Injections of MEL in the p.m. were completely ineffective in inhibiting either the growth of the gonads and adnexa or the pituitary Prl levels if the animals had been pinealectomized. Likewise, superior cervical ganglionectomy, decentralization of the superior cervical ganglia and anterior hypothalamic deafferetation, procedures which interfere with the sympathetic nerve supply to the pineal gland, negated the ability of p.m. MEL injections to inhibit reproduction in male hamsters. The results indicate that daily MEL injections are capable of suppressing reproductive physiology in male hamsters, but only when the indole is injected late in the light period, in this case, 13 h after light on. The findings also illustrate that daily p.m. MEL injections can inhibit reproduction only in animals that have an intact and sympathetically innervated pineal gland.

Animals↗

Prolactin-releasing and release-inhibiting factor activities in the bovine, rat, and human pineal gland: in vitro and in vivo studies.

The effects of crude extracts of bovine, rat, and human pineal glands on prolactin (PRL) release were studied using an in vitro system. In addition, the effects of a known pineal constituent, arginine vasotocin (AVT), and crude bovine pineal extract (bPE) on PRL secretion were studied in vivo. Normal male rat hemipituitaries (HP), incubated with bPE (13 mg tissue/HP)released 200%, 150%, and 285% more PRL into the medium than did their corresponding untreated control halves incubated in either Medium 199 alone, hypothalamic extract, or cerebral cortical extract, respectively. HP incubated with either rat (6 mg of tissue/HP) or human (25 mg of tissue/HP) pineal extract released 110% and 75% more PRL, respectively, than did their corresponding untreated control halves. HP exposed to 10 mg tissue eq of either bovine pineal fraction A1 or bovine pineal fraction A3 released 88% and 63%, respectively, less PRL than did their corresponding untreated control halves incubated in Krebs-Ringer Bicarbonate (KRB) medium. Quantitites of melatonin, thyrotropin-releasing hormone (TRH), or estrogen, comparable to those found in the pineal, had no significant effect on PRL secretion in vitro. The iv injection of either bPE (90 mg tissue/rat) or AVT (10 mug/rat) into estrogen and progesterone-treated male rats resulted in a 40% and 138% increase, respectively, in plasma PRL titers, 10 min after injection, over pre-injection control levels. The per cent of increase in plasma PRL levels in these animals was significantly greater than that observed in control rats receiving either saline or cortical extract. The results suggest that crude extracts of pineal glands of three different species contain prolactin-releasing factor (PRF) activity which is probably not due to any endogenous melatonin, TRH, or estrogen that may be present. Conversely, two bovine pineal fractions, A1 and A3, appeared to exhibit prolactin-inhibiting factor (PIF) activity. We have concluded that the pineal gland may serve as an alternate or supplemental source of PRF and/or PIF.

Aged↗

Dose-dependent prolactin releasing activity of arginine vasotocin in intact and pinealectomized estrogen-progesterone treated adult male rats.

Estrogen-progesterone (EP) treated adult male rats were injected intravenously (iv) with 0.1, 1 or 10 mug arginine vasotocin (AVT) or Ringers lactate solution. A significant dose-related rise in plasma prolactin was evident 10 min after injection with AVT. In a second experiment, sham-operated or pinealectomized EP-treated male rats were injected iv with 0.1 or 1 mug AVT or diluent. Plasma prolactin was significantly elevated in both sham-operated and pinealectomized groups at both 10 and 20 min post-injection of 1 mug AVT. These results indicate that AVT has prolactin-releasing activity and that this activity is not dependent upon the presence of an intact pineal gland.

Animals↗

Nocturnal elevation of plasma melatonin and urinary 5-hydroxyindoleacetic acid in young men: attempts at modification by brief changes in environmental lighting and sleep and by autonomic drugs.

In order to determine whether the human pattern of circulating melatonin resembles that previously described in lower animals, men 19-32 years old were exposed to a light-dark cycle with 14 hours of light per day (L:D 14:10). In whites and blacks, nocturnal (dark phase, sleeping) melatonin levels were almost always elevated to 0.05-0.1 ng/ml plasma compared with lower or undetectable levels during the day, measured by the tadpole bioassay. Thin-layer migration of bioactive material was identical to that for melatonin standard. A rhythm with nocturnal elevation of urinary 5-hydroxyindoleacetic acid (5-HIAA) was observed. Nocturnal (sleep phase) rise in blood melatonin (but not urinary 5-HIAA) continued during 21/2 day-night cycle lengths after the onset of constant light. Though the dark phase plasma melatonin rise was less marked after reversal of the sleep-wake cycle (no change in the light cycle), dark phase rise in urinary 5-HIAA continued. Though marked cardiovascular and other effects were produced by intravenous isoproterenol or scopolamine, no definite effect on melatonin levels was observed after either drug during the light phase in waking subjects.

Adult↗

Inhibition of human chorionic gonadotrophin-induced hypertrophy of the ovaries and uterus in immature mice by some pineal indoles, 6-hydroxymelatonin and arginine vasotocin.

Administration of the indoles 5-methoxytryptophol, 6-hydroxymelatonin, melatonin, N-acetylserotonin or 5-methoxyindole-3-acetic acid (six 100-mug injections given at intervals of 12 h) inhibited both the absolute and relative ovarian and uterine weights of immature female mice pre-treated with HCG. Administration of 5-hydroxytryptophol or 5-methoxytryptamine at the same dosage inhibited ovarian but not uterine hypertrophy in mice pre-treated with HCG.

Animals↗

Pineal influence on intermale aggression in adult house mice.

Previously isolated, adult male mice of a wild-derived strain were sham-operated or pinealectomized (pinx) and 14 days later were paired for 15 min, then grouped three per cage for 7 days. During 15 min pairings, mean latency to initiation of fighting was increased twofold and duration of fighting was reduced 35 to 41 percent in pairs comprised of one or both pinx animals. Although pinealectomy failed to influence which pair member initiated fighting, sham males were ranked as dominant in 75 percent of sham-pinx pairs. Pinealectomy reduced adrenal gland weights among isolated animals and increased in general the effects of social subordination in grouped males. Compared to sham subordinates, pinx subordinates experienced adrenal enlargment and twofold greater wounding and had lighter thymus glands and final body weights. Additionally, however, pinealectomy prevented atrophy of seminal vesicles among subordinates. Thus, present results suggest a role of the pineal gland in influencing intermale aggression and linking social stimuli with testis dysfunction in adult house mice.

Adrenal Glands↗

A counter antigonadotrophic effect of melatonin in male rats.

Blinding and anosmia in male rats is followed by retarded bodily development, reduced weights of the gonads and adnexa, and depressed levels of pituitary luteinizing hormone and prolactin. The effects of dual sensory deprivation are negated, for the most part, by either pinealectomy or the weekly subcutaneous implantation of melatonin (in beeswax). This is the first report that melatonin negates the antigonadotrophic influence of the rat pineal gland.

Adrenal Glands↗

Prolactin-releasing activity of arginine vasotocin in vitro.

A significant elevation in both luteinizing hormone (LH) and prolactin release was observed in the culture medium of hemipituitaries from castrated estrogen-progesterone (EP) primed female rats incubated for 5 h with arginine vasotocin (AVT) and luteinizing hormone-releasing hormone (LRH) compared to corresponding halves incubated with LRH alone. However, AVT alone did not significantly alter the discharge of LH or prolactin from hemipituitaries of EP-treated rats in vitro. Arginine vasopressin, a natural analogue of AVT, inhibited prolactin release using this same model system. Normal male rat hemipituitaries incubated with AVT released significantly more LH and prolactin into the culture medium than did their corresponding halves. A log-dose response curve indicated that any dose from 100 ng to 10 mug AVT significantly promoted prolactin release. However, the terminal tripeptide of AVT, Pro-Arg-Gly(NH2), failed to modify the discharge of LH or prolactin into the culture medium.

Animals↗

Studies on the minimal dosage of melatonin required to inhibit pineal antigonadotrophic activity in male golden hamsters.

Blinding adult male golden hamsters was followed by atrophy, within 12 weeks, of the testes and accessory sex organs (seminal vesicles and coagulating glands) and by a significant reduction in pituitary prolactin levels. In experiment 1 blind hamsters received subcutaneously implanted melatonin-beeswax (1:24 mg) pellets at the following intervals: once per week, per 2, 3, 4, 6 weeks, or only one pellet during the 12-week experimental period. The melatonin-beeswax pellets, regardless of the frequency of implantation, overcame completely the inhibitory effects of blinding on reproduction and nearly completely the depressant action of light deprivation on pituitary prolactin levels. In the second study the melatonin-beeswax pellets were implanted subcutaneously into blind hamsters every 2 weeks. The pellets contained either 1 mg, 500, 100, 50, or 1 mug melatonin. With the exception of the 1-mug dosage, melatonin again negated almost totally the inhibitory action of darkness on the gonads and accessory organs and also, for the most part, prevented the drop in pituitary prolactin levels. Based on these studies, when melatonin is chronically administered subcutaneously in a beeswax pellet the minimal dosage of melatonin required to counteract the inhibitory effect of darkness on reproduction seems to be less than 3.6 mug/day. The effects of chronic melatonin treatment are similar to those of pinealectomy.

Animals↗

Pineal methoxyindoles: new evidence concerning their function in the control of pineal-mediated changes in the reproductive physiology of male golden hamsters.

Maintaining adult male golden hamsters in short daily photoperiods (1hr of light and 23hr of darkness daily; LD 1.23) for 12 weeks caused the tests and accessory sex organs to atrophy and also led to significant depressions in pituitary LH and prolactin levels. If hamsters that were kept in LD 1.23 CYCLES RECEIVED WEEKLy subcutanceous implants of either a melanioninbeeswax or a 5-methoxtrypotophol-beeswax pellet (1 mgindole in 24 mg beeswax) the testes and accessory sex organs failed to involute and pituitary LH levels did not drop. Both treatments also retarded the depression in hypophyseal prolactin retarded the depression in hypophyseal prolactin levels. Treatment (twice daily on weekdays and once daily on weekends) with 1.5 mug injections of synthetic LRH (in 0.2 ml 8% gelatin) did not prevent gonadal or accessory organ atrophy while it further depressed hypophyseal LRH treatment, plasma LH titers were significantly elevated. The reproductive organs of hamsters that were moved from short (LD1;I 23) to long (LD 14;10) daily photoperiods regenerated within 8 weeks. This light-induced restoration of the gonads was not prevented or retarded by the weekly implantation of either melantonin-beeswax or 5-methoxytrptophol-beeswax pellets. The results suggest that in the male golden hamster neither melatonin nor 5-methoxtryptophol accounts for the antigonadotrophic activity of the pineal gland.

Animals↗

A study of indoles which inhibit pineal antigonadotrophic activity in male hamsters.

Blinding adult male golden hamsters led to involution of the testes and accessory sex organs (seminal vesicles and coagulating glands) and to a regression in pituitary prolactin levels within 8 weeks. The subcutaneous implantation of either melatonin or 6-hydroxymelatonin (1 mg/wk in beeswax) prevented the atrophy of the reproductive organs and the decrease in the stores of pituitary prolactin. Two other indoles, N-acetylserotonin and 5-hydroxytryptophol, failed to counteract the reproductive effects of blinding. Both melatonin and 6-hydroxymelatonin significantly elevated plasma LH titers.

Animals↗

Melatonin-pineal relationships in female golden hamsters.

Light deprivation by blinding in female hamsters was followed by a regression of the reproductive organs, an elevation of pituitary LH concentration and a depression of pituitary prolactin levels. Pinealectomy negated almost completely the effects of light deprivation on the neuroendocrine-reproductive axis. Weekly subcutaneous implants of a melatonin:beeswax pellet completely prevented the pineal gland from inhibiting reproductive physiology in blinded hamsters. The findings suggest that melatonin is not pineal antigonadotrophic factor in female golden hamsters. Melatonin implanted hamsters also had higher than normal levels of plasma prolactin.

Animals↗