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Biomedical subjects

M K Vaughan

Publications and source records attributed to M K Vaughan.

At least 109 records · Page 6Linked to original sources

Age-associated reduction in nocturnal pineal melatonin levels in female rats.

Pineal N-acetyltransferase (NAT) activity and radioimmunoassayable levels of melatonin were compared in 2-month-old (young), 12-month-old (middle-aged), and 29-month-old (old) female rats killed at 1600 h (during the light) and at 2300 h (4 h after darkness onset) and 0100 h (6 h after darkness onset). During the light period, NAT levels were equivalent in pineals from each age group. With the onset of darkness NAT levels rose sharply and were again equivalent in all groups at 2300 h. At 0100 h pineal NAT values in the old rats were lower than in the other two groups. Melatonin values were low in pineal glands of all animals killed at 1600 h in light. By 4 h after darkness onset pineal melatonin content in the young rats had increased 12-fold compared to a 6-fold rise in the old animals. Melatonin levels in the middle aged rats were intermediate between the other two groups. Similar relationships were observed in the rats killed at 0100 h. By this time the young rats had melatonin levels 17 times higher than during the day while the increase in the old rats was only 7-fold; 12-month-old rats again had intermediate levels. The finding show a marked reduction in pineal melatonin with aging in female rats.

Aging↗

Influence of pinealectomy on corticotropin (ACTH).

Sensory deprivation produced by removing the eyes and olfactory bulbs in male rats allowed pinealectomy to markedly augment the post-adrenalectomy elevation of ACTH levels. Pineal removal or sensory deprivation separately did not have this effect. Thus, intact sensory input and an intact pineal gland are independently capable of restricting the post-adrenalectomy rise in ACTH levels.

Adrenocorticotropic Hormone↗

Naloxone inhibits arginine vasotocin- (AVT) induced prolactin release in urethane-anesthetized male rats in vivo.

Arginine vasotocin (AVT) (1 microgram) elicited a two-fold increase in serum prolactin (Prl) levels 10 min following its i.v. injection into urethane-anesthetized adult male rats. At 20 min after AVT administration serum Prl concentrations had essentially returned to preinjection levels. Prior treatment of the animals with 0.2 mg/kg body weight of naloxone (Nal), an opiate antagonist, completely blocked the Prl response to a single injection of AVT. Nal itself did not alter the titers of Prl at any time point. The results suggest that the in vivo Prl-releasing effect of AVT is mediated via an interaction with opiate receptors.

Animals↗

Acute effects of arginine vasotocin on plasma and pituitary levels of prolactin in the male rat: influence of urethane anesthesia.

The acute effects of arginine vasotocin (AVT), a putative pineal peptide, on plasma levels of prolactin were investigated in the unanesthetized, estrogen-progesterone-treated male rat. A 10-microgram s.c. injection resulted in significantly increased levels of prolactin while a 1-microgram injection depressed plasma levels of this hormone; an inhibition of release was further suggested by increased levels of pituitary prolactin in rats treated with the lower dose. The same dose administered subcutaneously to urethane-anesthetized rats had no significant effect on plasma prolactin titers while a 10-microgram dose was still stimulatory. In anesthetized rats, no dose of the AVT administered (1 ng to 10 micrograms, s.c., or 1 fg to 1 microgram, i.v.) resulted in inhibition of prolactin release. In the unanesthetized normal male rat, 5 micrograms AVT first increased and then decreased levels of prolactin. Urethane anesthesia appears to mask an inhibitory effect of AVT on plasma prolactin levels in these animal preparations. Since AVT is capable of decreasing plasma prolactin levels, this peptide might be involved in the depression of plasma prolactin levels which appears to (at least partially) mediate pineal-induced gonadal degeneration.

Anesthesia↗

Interaction of luteinizing hormone-releasing hormone, cyproterone acetate and arginine vasotocin on plasma levels of luteinizing hormone in intact and castrated adult male rats.

Treatment of unanesthetized castrated adult male rats every 3 h for 48 h with either 5 microgram of arginine vasotocin (AVT) and/or 1 microgram luteinizing hormone-releasing hormone (LRH) caused a significant inhibition of plasma levels of luteinizing hormone (LH) and compared to castrated control rats receiving diluent only. However, the intravenous (iv) injection of 1 microgram of AVT into urethane-anesthetized male rats which had been castrated for 0, 24 or 48 h did not affect plasma levels of LH at 10, 20 or 60 min following injection compared to their respective diluent-treated castrated control rats. Similarly, the iv injection of either 100 ng, 1 microgram or 10 microgram AVT was unable to acutely affect plasma levels of LH in intact male rats. Following the iv injection of 2 doses of 50 ng LRH spaced 1 h apart in anesthetized castrated male rats, 2 peaks of equal magnitude in plasma LH were noted. Castrated rats treated with 2 injections spaced 1 h apart of LRH + AVT had significantly higher plasma levels of LH than did rats treated with LRH alone. In subsequent studies, both AVT and arginine vasopressin were observed to augment the plasma response of LH to an injection of LRH whereas oxytocin had no effect. A single injection of AVT + LRH significantly augmented the plasma titers of LH compared to levels observed in LRH-treated control rats as did a second injection 1 h later. The administration of cyproterone acetate sc for 2 days by itself had no effect on plasma LH but in conjunction with LRH caused a marked rise in plasma LH compared to intact rats treated with LRH alone. AVT in combination with LRH and cyproterone acetate caused a significant elevation in plasma LH at 60 min post-injection when compared to plasma levels of rats treated with LRH alone or the combination of LRH and cyproterone acetate. It is concluded that acute intravenous injections of AVT augment the LH-releasing activity of LRH; chronic treatment for 48 h, however, with LRH + AVT leads to a significant depression of plasma LH perhaps due to an exhaustion of the releasable pool of LH in the anterior pituitary.

Animals↗

The effect of subcutaneous injections of melatonin, arginine vasotocin, and related peptides on pituitary and plasma levels of luteinizing hormone, follicle-stimulating hormone, and prolactin in castrated adult male rats.

A sc injection of 2 micrograms arginine vasotocin (AVT) administered every 2 h for a 25-h period starting 1 h after castration of adult male rats caused a 43% reduction (P less than 0.05) in plasma levels of LH compared to diluent-treated castrated controls. In Exp 2, a sc injection of 5 micrograms AVT or diluent was administered to intact or acutely castrated male rats every 3 h for 48 h. After AVT administration, both plasma LH (P less than 0.001) and FSH (P less than 0.05) were significantly reduced, with a concomitant increase in pituitary levels of these gonadotropins. Using the same injection regimen in Exp 3, 250 micrograms melatonin had no effect on plasma or pituitary levels of LH in castrated male rats. In the fourth experiment, neither 1 IU arginine vasopressin nor 1 IU oxytocin had an effect on plasma or pituitary levels of LH, whereas 1 IU of AVT significantly lowered plasma levels of LH (P less than 0.05) and prevented the fall in the pituitary level of this gonadotropin (P less than 0.01) when compared to diluent-treated castrated control rats. Oxytocin (1 IU) significantly inhibited (P less than 0.01) plasma levels of FSH and raised plasma levels of PRL (P less than 0.01) in castrated male rats. No effect on plasma titers of PRL were observed after treatment of castrated rats with AVT in Exp 2 or 4. It is concluded that in acutely castrated male rats, AVT could possibly act either on the hypothalamus and/or the pituitary to affect pituitary and plasma levels of gonadotropins.

Animals↗

Interaction of daily injections and subcutaneous reservoirs of melatonin on the reproductive physiology of female Syrian hamsters.

This study investigated the ability of continuously available melatonin (from sc melatonin-beeswax pellets that were implanted bi-weekly) in overcoming the antigonadotrophic action of single daily melatonin (25 microgram) injections given late in the light period to female Syrian hamsters kept in light:dark cycles of 14:10. The melatonin-beeswax pellets contained either 1, 50, 500 microgram, 1 or 10 mg melatonin and 25 mg beeswax. Daily melatonin injections into hamsters implanted with beeswax only caused vaginal acyclicity in 60% of the animals within 6 weeks. After 10 weeks of treatment, uterine weights and pituitary levels of immunoreactive prolactin were still greatly depressed. Beeswax pellets containing either 500 microgram, 1 or 10 mg melatonin overcame the inhibitory effects of daily melatonin injections. Thus, the vaginal cycles and pituitary hormone levels of these animals were indistinguishable from those of untreated control animals. Beeswax pellets containing either 1 or 50 microgram melatonin were incapable of counteracting the antigonadotrophic effects of daily injections of melatonin. This is the first report that continuously available melatonin can negate the effects of daily injections of melatonin in female hamsters. When measured after 10 weeks, none of the treatment procedures significantly influenced circulating levels of luteinizing hormone or prolactin.

Animals↗

Diurnal variation in uterine estrogen receptors in immature female rats--inhibition by arginine vasotocin.

A diurnal variation in uterine estrogen receptors from immature female rats was observed with the peak occurring during the mid-light phase (noon) of the cycle. Although no dose response was noted, all concentrations of arginine vasotocin ranging from 5 x 10(-7) to 5 x 10(-9) significantly inhibited binding of 3H-estradiol to estrogen receptors in the cytosol fraction of uteri obtained from immature female rats either during the light or dark phase of the photoperiod.

Aging↗

Effect of several androgens, cyproterone acetate or estrogen-progesterone on the prolactin-releasing activity of arginine vasotocin in castrated male rats.

Intravenous (iv) administration of 5 microgram of arginine vasotocin (AVT) into urethane-anesthetized, castrated male rats had no effect on plasma prolactin titers as compared to the rise in prolactin levels observed in intact AVT-treated rats. However, when castrated rats were first treated for two days with 2.5 mg/day of testosterone propionate and then challenged with a 5-microgram dose of AVT, the prolactin surge values obtained were comparable to those seen in intact AVT-treated rats. Conversely, treatment of intact rats for two days with 25 mg/day of the anti-androgen, cyproterone acetate, blocked the prolactin-releasing activity of AVT. In a separate experiment, treatment of castrated rats for two days with 2.5 mg/day of testosterone, androsterone or 50 microgram of estradiol benzoate and 25 mg progesterone, completely restored the prolactin-releasing activity of AVT. Similar treatment with 2.5 mg/day of androstenedione or dihydrotestosterone was without effect in restoring this response to AVT. It is concluded that the presence of gonadal steroids is essential to the action of AVT in provoking the release of prolactin in urethane-anesthetized male rats.

Androgens↗

Effects of melatonin and natural and synthetic analogues of arginine vasotocin on plasma prolactin levels in adult male rats.

A significant elevation in plasma prolactin was observed 10 min following the intravenous injection of 100 microgram of melatonin into either estrogen-progesterone (EP) primed or into nonsteroid-treated male rats. 60 min postinjection in the EP primed rat, the groups treated with 100 microgram or 10 mg of melatonin had signficantly elevated plasma prolactin levels while no effect was observed with these same doses in the nonsteroid-treated rats. Compared to diluent-treated controls, a significant elevation in plasma prolactin was observed at 10, 20 and 60 min following the intravenous injection of either 1 microgram arginine vasotocin (AVT) or 1 mg melatonin into EP primed male rats. A consistent rise in plasma prolactin was also evident after the injection of 1 microgram of either arginine vasopressin, lysine vasopressin or AVT. Oxytocin had no effect on plasma prolactin values. The intravenous administration of 1 microgram of (deamino-1,6 dicarba, 8-arginine)-vasotocin caused a significant elevation of plasma prolactin 10 and 20 min after injection. However, the injection of another analogue of AVT, (4-leucine, 8-arginine)-vasotocin, had no effect on prolactin release at the time points measured.

Animals↗

The effects of arginine vasotocin on pregnant Mare's serum-induced ovulation in the immature female rat.

Arginine vasotocin (AVT) treatment (1 microgram/injection) every two hours beginning at 06.00 h on the morning preceding expected ovulation significantly inhibited ovulation in 29-day-old immature female rats treated 2 days earlier with 30 IU of PMS. Pre-ovulatory plasma surges and pituitary decreases in LH, FSH and prolactin as measured by radioimmunoassay were not eliminated by AVT treatment. However, there appeared to be an early rise in plasma FSH in these rats and the maximum plasma LH value attained during the surge period in PMS-treated rats was elevated by AVT treatment. Arginine vasotocin significantly inhibited the increase in ovarian weight which occurs in PMS-treated rats on the day preceding ovulation and uterine weights were consistently depressed in AVT-treated rats. The results of this study indicate that AVT likely inhibits PMS-induced ovulation at the level of the ovary, although the possibility cannot be ruled out that inhibition resulted from the advancement of the plasma FSH rise. These data and other studies investigating the effects of AVT on reproduction indicate that AVT is possibly capable of acting at more than one level of the hypothalamo-hypophyseal-gonadal axis.

Animals↗

Subcutaneous melatonin implants inhibit reproductive atrophy in male hamsters induced by daily melatonin injections.

Daily afternoon (at 7 p.m.) injections of melatonin (25 microng in oil) into adult male hamsters for 50 days led to atrophy of the testes and accessory sex organs (seminal vesicles and coagulating glands) and in a significant depression in pituitary LH and prolactin content and concentration. These actions of melatonin were prevented if the animals had been pinealectomized before the daily melatonin injections were begun. Likewise, if hamsters received a weekly subcutaneous implant of melatonin in beeswax (1 mg melatonin in 24 mg beeswax) the daily melatonin injections failed to inhibit the growth of the reproductive organs and to depress pituitary LH and prolactin levels. Beeswax by itself had no such effect.

Animals↗

Stimulation of rat prolactin secretion in vivo by arginine vasotocin: influence of age of solution, nighttime administration, and dose.

In male rats pretreated for 3 days with 50 microgram of estradiol benzoate (E) and 25 mg of progesterone (P), the i.v. administration of 1 microgram of arginine vasotocin (AVT) from solutions that were 0, 6, 24 or 48 h old caused a significant rise in plasma prolactin (Prl) 10 min after injection. In the 2nd experiment, the i.v. injection of 1 microgram AVT into EP-primed adult male rats at either 01:00 (during darkness) or 13:00 h (during light) resulted in a significant and similar elevation in plasma Prl levels. In the 3rd experiment, normal adult male rats under urethane anaesthesia were given an i.v. injection of diluent or of 100 ng, 1 microgram or 10 microgram AVT. A significant rise in plasma Prl was observed at 10 and 20 min following injection only in the group treated with 1 microgram AVT. In none of these experiments did AVT alter the content of pituitary Prl.

Animals↗