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Biomedical subjects

B D Goldman

Publications and source records attributed to B D Goldman.

At least 91 records · Page 5Linked to original sources

Hormonal regulation of the annual pelage color cycle in the Djungarian hamster, Phodopus sungorus. II. Role of prolactin.

This study investigated whether photoperiod-induced changes in circulating prolactin levels, which have been observed in the Djungarian hamster ( Yellon and Goldman, '83; Duncan and Goldman, ' 83a ), might be involved in seasonal pelage color changes in this species. Injection of ovine prolactin (100 micrograms/day) inhibited the short photoperiod-induced winter molt. This finding indicated that the suppression of endogenous prolactin levels normally occurring in short photoperiod-housed hamsters (Duncan and Goldman, ' 83a ) may induce the winter molt. Suppression of prolactin secretion with bromoergocryptine (200 micrograms/day) strongly inhibited the spring molt, while concomitant treatment with ovine prolactin (100 micrograms/day) overcame this effect of bromoergocryptine. Injection of bromoergocryptine (200 micrograms/day) stimulated the winter molt in castrated hamsters housed in long photoperiod; concomitant injection of prolactin (100 micrograms/day) reversed this effect as well. These findings strongly suggested that an increase in endogenous prolactin levels may be necessary for the development and maintenance of the summer pelage.

Animals↗

Male hamster investigatory and copulatory responses to vaginal discharge: relationship to the endocrine status of females.

The ability of vaginal discharge from ovariectomized (OVEX) or hypophysectomized (HYPOX) female hamsters to elicit intense genital investigation and to facilitate overt copulatory behavior in males was compared with that of estrous vaginal discharge. The discharges were collected by vaginal lavage with water. In order to avoid exposure of experimental males to female stimuli other than vaginal discharge, the behavioral tests employed anesthetized males (female surrogates) whose hindquarters were scented with the collected vaginal material or with control solvent (water). Both the OVEX and HYPOX discharges elicited intense genital investigation and significantly increased the incidence of intromission attempts toward the scented surrogates. However, both types of discharge had significantly less behavioral activity than estrous vaginal discharge. In a subsequent experiment, a water dilution series of estrous vaginal discharge was tested for the ability to promote genital investigation and copulatory behavior toward scented surrogates. The amount of discharge typically extruded by one estrous female in response to tactile genital stimulation can be diluted one hundred-fold without appreciable reductions in its behavioral activity. These results demonstrate that the behavioral activity of hamster vaginal discharge is related to the endocrine status of females, and suggest that previous failures to demonstrate clear dependence on ovarian function might have been due to ceiling effects in laboratory tests.

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Hypothalamic deafferentation inhibits the stimulatory influence of prolactin on follicle-stimulating hormone release in the golden hamster.

We have examined the effects of PRL-producing ectopic pituitary grafts on plasma FSH and LH levels in male golden hamsters with anterior (AHD) and anteolateral hypothalamic deafferentation (ALHD). After hypothalamic deafferentation or sham deafferentation, hamsters received pituitary transplants under the kidney capsule. In the first experiment, the animals were unilaterally nephrectomized 5-6 weeks after transplantation to remove the ectopic pituitaries. In a second experiment the ectopic pituitaries remained under the kidney capsule for the duration of the experiment. Serial blood samples were collected before and after pituitary transplantation and after transplant removal. In the first experiment, ALHD resulted in a significant (P less than 0.01) suppression of plasma LH levels that lasted through the entire study, but had no significant effect on plasma FSH levels or on testicular and seminal vesicle weight. The presence of pituitary grafts resulted in a significant (P less than 0.01) elevation in plasma FSH levels in the sham-deafferented hamsters but had no effect on plasma FSH levels in those with ALHD. After transplant removal there was a significant (P less than 0.01) drop in plasma FSH levels in the hamsters that had been sham deafferented but not in those with a deafferented hypothalamus. Plasma LH levels were not affected by the pituitary transplants or their removal in either group. In the second experiment, ALHD but not AHD significantly (P less than 0.05) reduced testicular and seminal vesicle weights. Transplantation of an anterior pituitary elevated plasma FSH levels in the control group but not in the AHD and ALHD groups. Both types of deafferentations suppressed plasma LH levels below the limit of sensitivity of the assay for the duration of the experiment. Plasma PRL levels were markedly elevated only in the groups with an ectopic pituitary transplant. These results suggest that the anterior connections of the medial basal hypothalamus are necessary in order for PRL-producing pituitary transplants to influence FSH secretion from the in situ pituitary.

Afferent Pathways↗

Photoperiod control of reproductive development in the male Djungarian hamster (Phodopus sungorus).

The Djungarian or Siberian hamster (Phodopus sungorus) is a seasonally breeding rodent in which maturation of gonadal function depends upon the photoperiod during rearing. It was hypothesized that the ability of short days to block testicular growth resulted from insufficient gonadotropin secretion during critical stages of development. This question was studied by measurement of serum concentrations of FSH, LH, PRL, and androgens by RIA systems validated for use in this species. Males reared from birth in long (16 h of light, 8 h of darkness) or short (10 h of light, 14 h of darkness) photoperiods were killed at 5- to 10-day intervals between 5 and 60 days of age. Regardless of photoperiod before 15 days of age, body and testes weights similarly increased. Serum concentrations of FSH and PRL gradually increased during this age period, although PRL concentrations were statistically higher in males under long days compared to those under short days. Circulating serum LH and androgen levels were high before 10 days of age, but decreased by 15-20 days of age in both photoperiods. Under long days, the period between 15 and 30 days of age was characterized by rapid body (1 g/day) and testicular (10-38 mg/day) growth, peak serum FSH concentrations (20-25 days), sustained elevation in serum LH and androgen concentrations, and further increases in serum PRL values. After 30 days of age, a reduced growth rate for body and testes occurred; serum FSH levels declined, while adult serum concentrations of LH, PRL, and androgens were attained. In contrast, hamsters exposed to short days from birth exhibited a slower rate of body and testicular growth by 20 days of age. Short days blocked peak FSH secretion and suppressed serum concentrations of LH and androgens after 20 days of age. PRL titers were significantly lower in short day compared to those in long day housed hamsters at all ages. These results support the hypothesis that the short day-induced suppression of gonadotropins and PRL secretion during development blocked gonadal maturation.

Aging↗

Effects of timed melatonin infusions on reproductive development in the Djungarian hamster (Phodopus sungorus).

In confirmation of earlier work, daily melatonin infusions of 9- or 12-h duration inhibited testicular development in pinealectomized juvenile Djungarian hamsters, while daily infusions of 6-h duration did not prevent gonadal growth. Two other methoxyindoles (5-methoxytryptophol and 5-methoxytryptamine) had less than 4% of the activity shown by melatonin. When pinealectomized hamsters received two short duration (i.e. 3, 5, or 6 h) melatonin infusions each day, gonadal development was not inhibited if the two daily infusions were separated by a period of 2 or 3 h without melatonin treatment. Thus, the effects of separate pulses of melatonin were not additive in this paradigm. When single, short duration daily infusions of melatonin (5-h) or isoproterenol (6-h) were administered to pineal-intact hamsters, gonadal inhibition occurred only when the infusions were given at times that would lead to an expected overlap with and extension of the endogenous nocturnal melatonin peak. Significant inhibition of testicular growth could be obtained with as few as 2-4 days of melatonin treatment. These observations further support the importance of melatonin peak duration and also indicate other interesting temporal aspects of melatonin action in the Djungarian hamster.

Aging↗

Does prolactin modify testosterone feedback in the hamster? Pituitary grafts alter the ability of testosterone to suppress luteinizing hormone and follicle-stimulating hormone release in castrated male hamsters.

Adult male golden hamsters maintained in a long photoperiod (14 h of light and 10 h of darkness) or in a short photoperiod (5 h of light and 19 h of darkness for 7 weeks) were castrated and either given one anterior pituitary transplant under the kidney capsule or sham-operated. Additional animals were castrated and grafted or sham-grafted at the time of transfer to the short photoperiod. Starting 2 weeks after castration, all animals were injected three times a week with 20 micrograms testosterone propionate (TP). After 3 weeks, the dose of TP was increased to 80 micrograms and, after an additional 2 weeks, to 320 micrograms per injection. Blood samples were collected 2 weeks after castration and 1 day after the last injection of 20, 80, and 320 micrograms TP. Short photoperiod reduced and pituitary grafts increased plasma PRL levels. Plasma testosterone levels were related to the dose of injected TP, but were not influenced by photoperiod or pituitary transplants. Before the onset of TP injections, plasma LH and FSH levels in grafted and sham-grafted hamsters did not differ. In each of the three photoperiod conditions, injections of TP were consistently less effective in suppressing plasma gonadotropin levels in pituitary-grafted animals than in sham-grafted controls. These results indicate that PRL modulates the effects of exogenous testosterone on LH and FSH release in adult castrated male golden hamsters, this effect of PRL is due to reducing the sensitivity of the hypothalamic-pituitary system to feedback inhibition by testosterone, and suppression of pituitary PRL release in short photoperiod may be partially responsible for the concomitant increase in the sensitivity of LH and FSH release to inhibition by testosterone.

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Circadian organization of locomotor activity in the Turkish hamster (Mesocricetus brandti).

The circadian organization of locomotor activity was examined in Turkish hamsters while exposed to a light-dark (LD) cycle, constant illumination (LL), and following blinding and gonadectomy. Under LD 16:8 the activity rhythm of all hamsters became well entrained with activity beginning approximately 30 min after dark onset. In contrast, when activity rhythms free-ran as the result of exposure to LL or blinding, a variety of spontaneous perturbations in the period and/or phase of the activity rhythm were observed.

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Effects of short photoperiod on the ability of golden hamster pituitaries to secrete prolactin and gonadotropins in vitro.

Transfer of male golden (Syrian) hamsters from a 14L:10D (light:dark) to a 5L:19D photoperiod induced significant changes in pituitary function tested in vitro. Within 27 days after transfer to a 5L:19D photoperiod, basal prolactin (Prl) release was significantly depressed and response to dopamine (DA) was significantly enhanced as compared to Prl release by pituitaries from 14L: 10D hamsters. Follicle-stimulating hormone (FSH) release tended to be depressed after 9 or 27 days of 5L:19D exposure, but the effect was not significant. After 77 days of 5L:19D exposure, Prl release was further suppressed, while FSH release surpassed that seen in 14L:10D pituitaries. In vitro FSH response to luteinizing hormone releasing hormone (LHRH) was also enhanced at this time. After 15 weeks of exposure to a short photoperiod, FSH secretion was still elevated above control levels, but Prl release and Prl response to DA were no longer different from that of 14L: 10D controls. Secretion of luteinizing hormone (LH) in vitro, either basal or LHRH stimulated, was not affected by photoperiod at any time tested. From these results, we conclude that short photoperiod exposure does not reduce the pituitary's ability to secrete LH or FSH, although secretion of Prl is severely attenuated.

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The pineal gland and mammalian photoperiodism.

The mammalian pineal gland appears to be a major endocrine component in the regulation of photoperiodic responses. The circadian pattern of secretion of the pineal hormone, melatonin, is regulated by the nervous system. Changes in photoperiod, acting via the nervous system, alter the temporal pattern of melatonin secretion. The changes in secretion pattern convey information about daylength from neural components of the circadian system to the reproductive system, and probably to other physiological systems.

Animals↗

Antigonadal effects of timed melatonin infusion in pinealectomized male Djungarian hamsters (Phodopus sungorus sungorus): duration is the critical parameter.

To determine which parameter of the day/night pattern of pineal melatonin secretion is the critical component signaling daylength information in the Djungarian hamster, we have developed a method for giving timed sc melatonin infusions in pinealectomized juvenile males. When given for 12 h daily, as little as 10 ng melatonin (14 pg/min) consistently induced testicular regression within 12 days. However, 10 ng melatonin infused for 4 or 6 h daily did not inhibit gonadal development. The effects of these infusions on the reproductive system did not depend on the time of day at which melatonin was administered. In complementary experiments, the minimal daily infusion duration and the critical daylength for induction of testicular regression were determined. The critical length of infusion (7-8 h) was in close agreement with the estimated duration of melatonin secretion during the critical scotophase. These findings support the hypothesis that melatonin mediates the pineal-antigonadal effects of short day exposure in the Djungarian hamster. Furthermore, the data strongly suggest that duration is the feature of nighttime melatonin release that is most important for photoperiodic time measurement in this species.

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Progonadal role of the pineal in the Djungarian hamster (Phodopus sungorus sungorus): mediation by melatonin.

A progonadal role of the pineal in both adult and juvenile male Djungarian hamsters has been demonstrated which confirms and extends previous reports. In short day-raised hamsters, stimulation of testicular development was achieved by transfer to long days. This stimulatory effect of long days was blocked by pinealectomy. Gonadal stimulation could be elicited in pinealectomized juveniles by timed daily infusions of melatonin. When given for 4 or 6 h daily at a dose rate of 0.83 or 83 ng/h, melatonin infusions stimulated testicular development and body growth. Measurement of plasma FSH and PRL indicated that this pubertal response resulted at least in part from a stimulatory effect of melatonin on the secretion of these hormones. Longer duration infusions (8 or 12 h) did not stimulate testicular development or body growth, and plasma FSH and PRL levels remained low. The efficacy of the short duration infusions did not appear to depend upon the time of day of administration. These findings are in close agreement with those of a previous study which investigated the antigonadal effect of long duration melatonin infusions. The present results demonstrate that melatonin administration can mimic the progonadal effects of the pineal in this species and add further support to the hypothesis that the pineal influences the reproductive system through changes in the duration of daily melatonin production.

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Relationship of the length of exposure to short photoperiod to the effect of prolactin on pituitary and testicular function in the golden hamster.

Adult male golden hamsters were given ectopic pituitary transplants at the time of transfer from a long (stimulatory) photoperiod (14 h L:10 h D) to a short photoperiod (5L:19D) or at various intervals thereafter. Grafts given at the time of transfer to 5L:19D failed to maintain plasma FSH levels significantly above those observed in sham-operated controls or to prevent regression of the testes. Grafts given after 4 weeks in 5L:19D increased plasma FSH levels and significantly diminished the decrease in testicular volume. Grafts given 14 weeks after transfer to 5L:19D caused a modest increase in plasma FSH levels and did not significantly alter the time course of testicular redevelopment. Similarly, grafts given 18 weeks after transfer to 5L:19D had no effect on testicular weight measured 2.5 weeks later. These results indicate that the ability of prolactin (secreted by the grafted pituitary) to increase testicular size and the responsiveness of the hypothalamic-pituitary system to prolactin gradually increase during short photoperiod-induced testicular regression, are maximal when the testes are fully regressed and decrease again during spontaneous redevelopment of the testes. We suggest that the effects of prolactin on the testes in golden hamsters are partly mediated by prolactin-induced stimulation of FSH release from the in-situ pituitary.

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Alterations in neuroendocrine function during photoperiod induced testicular atrophy and recrudescence in the golden hamster.

Transfer of golden (Syrian) hamsters from a 14L:10D (Light:dark) to a 5L:19D photoperiod causes profound changes in the reproductive axis. Testicular weight fell within 7 weeks of short photoperiod exposure and remained low until 19 weeks, at which time spontaneous recrudescence began. Plasma LH, FSH, and Prl levels were undetectable at 7.5 weeks of exposure, but LH and FSH returned to basal levels by 15 weeks and Prl by 20.5 weeks. Hypothalamic LHRH levels increased concurrently with the fall in LH and FSH, suggesting that LHRH release was decreased. Increasing plasma gonadotropin levels and testicular recrudescence were associated with decreases in hypothalamic LHRH content. Hypothalamic norepinephrine (NE) turnover was low at 10 weeks, suggesting that decreased LH and FSH levels were ultimately due to decreased adrenergic activity. At 15 weeks, plasma LH levels and hypothalamic NE turnover were both increased over values seen at 10 weeks. Hypothalamic dopamine turnover, possibly reflecting decreased Prl feedback, was decreased between 0 and 10 weeks, but returned to control level by 15 weeks. It, therefore, appears that the endocrine changes associated with photoperiod induced testicular regression and recrudescence are secondary to changes in hypothalamic function.

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Role of the testis in regulating the duration of hibernation in the Turkish hamster, Mesocricetus brandti.

The effect of castration on hibernation was studied in male Turkish hamsters (Mesocricetus brandti). In the first study the animals were exposed to a long-day photoperiod from birth and throughout the period of hibernation. Hibernation was induced by exposure to cold (10 degrees C). Intact males usually hibernated for approximately 6-7 months and then became euthermic. Males which had been castrated prior to cold exposure continued to hibernate for a longer period. None of the 6 surviving castrated males terminated hibernation by 8 months. Four of these animals survived for more than 2.5 years and continued to hibernate throughout this time. In a second study, hamsters were exposed to a short-day photoperiod to induce testicular regression prior to cold exposure. Most of the intact males again hibernated for 6-7 months while castrated hamsters remained in hibernation for 8-9 months. Thus, in both studies, castration prolonged the hibernation "season." In the second study, the testes, which had regressed in response to exposure to short days, underwent recrudescence in hibernating males at 5-7 months after the initial exposure to short days. A similar time course of testicular recrudescence was displayed by males housed under short days but not exposed to cold. These latter animals remained euthermic throughout the experiment. Thus, it appears that the duration of the seasonal testicular cycle, induced by exposure to short days, was affected little, if at all, by environmental temperature or by body temperature. The testicular cycle appears to influence hibernation, probably through changes in androgen secretion.

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Hibernation in the female Turkish hamster (Mesocricetus brandti): an investigation of the role of the ovaries and of photoperiod.

The possible role of the ovaries in hibernation was examined by comparing patterns of hibernation in intact and ovariectomized Turkish hamsters (Mesocricetus brandti). Ovariectomy had little, if any, effect on hibernation in these studies. However, females which were anovulatory prior to cold exposure entered hibernation more rapidly as compared to cycling females. Most females (both intact and ovariectomized) maintained in short days returned to a second phase of hibernation several months after terminating the initial phase. In contrast, most females housed in long days failed to show a second phase of hibernation. Thus, it is possible that effects of day length may be more important than effects of ovarian hormones in regulating hibernation in the female Turkish hamster.

Animals↗

Pineal melatonin in the Djungarian hamster: photoperiodic regulation of a circadian rhythm.

The pineal melatonin rhythm has been proposed to represent a physiological signal which mediates the effects of photoperiod in a variety of seasonal breeding mammals. Studies in other species have led to the hypothesis that an endogenous circadian mechanism controls pineal melatonin content and can adapt the melatonin rhythm to reflect shifts in the prevailing light-dark schedule. In this report, photoperiodic regulation of the pineal melatonin content was investigated in the male Djungarian hamster, a species that is a long day breeder and photo-periodic from early life. In the first study, a daily pineal melatonin rhythm persisted after 6-8 weeks of constant dark conditions in a specific phase relationship to the onset of wheel running activity. Pineal melatonin levels increased around the time of activity onset, and high values persisted for 14-17 h. In subsequent studies, adult males [previously maintained under long days (16 h of light and 8 h of darkness)] were subjected to one of three conditions: 1) a 3-h advance in the onset of darkness, 2) a delay in the time of light onset, or 3) both alterations in the photoperiod. The acute 3-h advance in onset of the dark period caused an earlier rise in pineal melatonin production by approximately 1.5 h compared to that in controls. In contrast, the falling phase of the pineal melatonin rhythm was not altered by extension of the dark period. Therefore, aspects of the pineal melatonin pattern, i.e. the rising phase and peak duration, reflected changes in the photoperiod, while the falling phase anticipated the onset of the light period predicted by the previous light-dark schedule. These observations support the hypothesis that melatonin production by the pineal is an endogenous circadian rhythm and, as a physiological signal, may convey information about the daylength.

Animals↗

Pineal is required for testicular maintenance in the turkish hamster (mesocricetus brandti).

The effect of pinealectomy on reproductive function was examined in the Turkish hamster, Mesocricetus brandti. Pinealectomy resulted in testicular regression in this species. This result was unexpected since pinealectomy prevents short day-induced regression of the gonads in the closely related Syrian hamster, Mesocricetus auratus. Decentralization of the superior cervical ganglia and exposure to continuous illumination also caused testicular regression in the Turkish hamster. These manipulations are believed to block pineal melatonin synthesis. In each case (i.e. pinealectomy, decentralization of the superior cervical ganglia, exposure to continuous illumination), the testes regressed after approximately 3--9 weeks and underwent recrudescence after approximately 16--28 weeks. This cycle of testicular regression and recrudescence was similar to that observed in Turkish hamsters exposed to a short day photoperiod. In further experiments, the effects of exogenous melatonin were studied in Turkish and Syrian hamsters. The results of these studies suggest that, in Turkish hamsters, pineal melatonin may be involved in both the maintenance of testis function during exposure to a long day photoperiod and also in the suppression of reproductive function in short days. This is in contrast to the Syrian hamster, in which melatonin appears to be important only for inhibition of gonadal function in short days.

Animals↗