Linda Y. Johnson

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.

Melatonin: Its Inhibition of Pineal Antigonadotrophic Activity in Male Hamsters

Exposure of male hamsters to short daily photoperiods (1 hour of light and 23 hours of darkness daily for 9 weeks led to total involution of the testes and accessory sex organs (seminal vesicles and coagulating glands). Pituitary levels of immunoreactive prolaction also decreased by about 60 percent after dark exposure. The inhibitory effects of darkness on the reproductive organs were prevented either by pinealectomy or by the subcutaneous implantation of a melatonin-beeswax pellet into the animals each week. Both pinealectomy and melatonin treatment also returned pituitary levels of prolactin toward normal. The results suggest that melatonin is not the pineal antigonadotrophic factor in the male golden hamster.

Variation in pineal melatonin content during the estrous cycle of the rat

Abstract Pineal levels of melatonin exhibit a circadian rhythm in the rat. To determine if this rhythm varies during the estrous cycle, adult rats were sacrificed every 2 hr from 2000 hr (prior to lights off) until 0800 hr (2 hr after lights on) throughout each day of the 4-day estrous cycle. Pineal glands were assayed for melatonin by radioimmunoassay. A significant circadian rhythm in the pineal content of melatonin was evident each day of the cycle with peak levels exhibited during the dark phase. There were significant differences in titers of melatonin present at 0200, 0400, and 0600 hr between various stages of the cycle. In general, highest nighttime levels occurred during the evenings of metestrus and diestrus, with levels at a minimum on the evening of estrus. These data indicate that the circadian pineal melatonin rhythm is a function of estrous cycle stage in the rat, and, thus, important differences exist in the pineal biosynthetic dynamics of this species relative to those of seasonal breeders such as the hamster and sheep. Additionally, the results suggest that hydroxyindole-O-methyltransferase, and not serotonin N-acetyltransferase, is the regulatory enzyme responsible for these estrous stage differences in pineal melatonin content.

Pineal biosynthetic activity and neuroendocrine physiology in the aging hamster and gerbil

Abstract The effects of advancing age on the ability of the pineal gland to produce melatonin and on the neuroendocrine physiology of Syrian hamsters and Mongolian gerbils were investigated. In 2-month-old male and female hamsters the nocturnal rise in pineal melatonin levels is on the order of 8-fold. As hamsters age the nighttime increases become progressively more depressed until in 18-month-old animals the nighttime rise in pineal melatonin is only twice the levels measured during the daylight hours. In male gerbils, the normal nocturnal increase in pineal melatonin levels observed in 2-month-old animals has completely disappeared by the time gerbils reach 19 months of age. The results suggest a marked reduction in pineal biosynthetic activity as animals age. In hamsters, neither hypothalamic norepinephrine nor dopamine levels were altered in 18-month-old animals compared to those in hamsters killed 8 weeks after birth. The reproductive system of both male and female hamsters and male gerbils seem to function relatively normally until the animals are 1 1 2 years old. Thus, the majority of the 18-month-old female hamsters exhibit normal vaginal cyclicity. Likewise, the patterns of gonadotrophin and prolactin secretion are quite similar to those in the young females. At the light microscope level, most of the ovaries of the old hamsters, like those of the young animals, were found to contain pre-antral and antral follicles and corpora lutea. The uteri of the old hamsters exhibited the most pronounced changes. There was an obvious paucity of endometrial glands and the submucosa appeared fibrous. The testes of neither the old (18 month) hamsters nor the old (19 month) gerbils appeared greatly different from those of the young animals. Likewise, in advancing age there were no marked effects on circulating levels of gonadotrophins and prolactin in male hamsters. Finally, old male gerbils had plasma levels of testosterone similar to those observed in much younger 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.

Depressant Action of the Pineal Gland on Pituitary Luteinizing Hormone and Prolactin in Male Hamsters

Blinding adult male hamsters either by bilateral orbital enucleation or by surgical removal of the inner retinal layers (ganglion cell layer, bipolar cell layer and rod cells) caused atrophy of the te

Effects of Melatonin on Thyroid Physiology of Female Hamsters

The effects of melatonin administration on thyroid physiology of female hamsters was investigated. A protocol of 25 micrograms given daily as subcutaneous injections late in the light period was found to inhibit blood levels of thyroxin (T4), triiodothyronine (T3) and thyrotropin (TSH). The free T4 index (FT4I) and the free T3 index (FT3I) were also significantly inhibited by melatonin injections. Decreasing the photoperiod under which the hamsters were kept, from 14 h light/10 h dark (14L/10D) to 10L/14D also resulted in decreased blood levels of these hormones. A protocol of melatonin injections using 2.5 mg daily, on the other hand, did not significantly inhibit blood levels of thyroid hormones or TSH; injection of this dose every afternoon into hamsters in long photoperiod significantly augmented the blood levels of T4. Continuously available melatonin in the form of subcutaneous implants of 1 mg melatonin in beeswax did not inhibit blood levels of thyroid hormones; furthermore, such implants prevented the inhibitory effects of injections of 25 micrograms melatonin. The results are consistent with the hypothesis that melatonin interferes with neurotransmitters which influence the synthesis or release of hypothalamic thyrotropin-releasing hormone.

Chronic exposure to short photoperiod inhibits free thyroxine index and plasma levels of TSH, T4, triiodothyronine (T3) and cholesterol in female syrian hamsters

1. Chronic exposure of female Syrian hamsters (Mesocricetus auratus) for 9 weeks to a short photoperiod (10L:14D) depressed the pituitary-thyroid axis as indicated by a drop in circulating titers of thyroid stimulating hormone (TSH), thyroxine (T4), triiodothyronine (T3) and the free thyroxine index (FT4I) compared to animals maintained under long photoperiodic conditions (14L:10D). 2. Short day treatment also reduced plasma cholesterol levels. 3. Neither plasma triglycerides, glucose nor growth hormone (GH) levels differed between hamsters exposed to short or long daily photoperiods.

Pineal Regulation of Immunoreactive Luteinizing Hormone and Prolactin in Light-Deprived Female Hamsters*

The influence of light deprivation pinealectomy and pineal denervation on pituitary and plasma levels of luteinizing hormone (LH) and prolactin in 62 adult female hamsters was studied. 46 of the hamsters were blinded by bilateral orbital enucleation. 10 of the blinded animals were pinealectomized and 11 were superior cervical ganglionectomized. After 8 weeks 12 blinded and 8 intact hamsters received 4-mcg LH-releasing hormone (RH)/day for 1 week after which all animals were necropsied. Immunoreactive LH and prolactin levels were determined by double antibody radioimmunoassays. The blinded hamsters had significantly higher levels of LH within the pituitary than the normal controls (p less than .001). Pituitary prolactin levels in the blinded were significantly decreased (p less than .001). LH-RH treatment did not markedly alter LH or prolactin levels in the pituitary. Plasma LH of the blinded hamsters was about twice as high as the controls. LH-RH did significantly raise plasma LH in the intact and blinded (p less than .01 and p less than .02 respectively). Blinded hamsters that were pinealectomized or ganglonectomized had LH and prolactin levels comparable to the controls. Plasma prolactin levels were only slightly altered among the 6 experimental groups.

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.