Gonadal Atrophy Research Articles

Effects of melatonin and thyroxine treatment on reproductive organs and thyroid hormone levels in male hamsters.

The effects of exogenous thyroid hormone administration on melatonin-induced gonadal atrophy were studied in young adult male hamsters. Animals were given daily afternoon injections of 25 micrograms melatonin and/or thrice-weekly injections of 7 micrograms thyroxine. A control group received injections of saline vehicle only. No significant effect of either treatment was seen on body weight. Melatonin-treated animals had significantly reduced testicular and seminal vesicle weights, compared with vehicle-treated control animals: serum T4 levels and the FT4I were reduced by melatonin treatment, but serum T3 and the FT3I were increased. No effect of melatonin was seen on in vitro T3 uptake. Thyroxine treatment alone, while leading to elevated serum T4 levels and FT4I, had no effect on T3, the FT3I, or T3 uptake. Thyroxine treatment normalized circulating T4 levels and the FT4I in melatonin-treated animals, without preventing the melatonin-induced testicular regression. The results are taken as evidence that the inhibitory effects of melatonin on gonadal and thyroid function are independently mediated.

The influence of light of different wavelengths on the methylating capacity of the pineal gland of male golden hamsters in relation to reproduction

In the present experiments the influence of light of different wavelengths on pineal indole metabolism in relation to reproduction was studied. Therefore, during autumn and winter male golden hamsters were kept under natural conditions but for the sunlight which was filtered exposing the hamsters to either normal (control), red or blue light. During the gradually shortening photoperiod at the start of the experiments under normal light conditions, a marked decrease of FSH and LH plasma content as well as testicular weight was found, indicating the onset of gonadal atrophy. During this period a high synthesis of 5-methoxytryptophan (MW) and 5-methoxytryptamine (MT) was determined. The synthesis of other 5-methoxyindoles (MI) was low, while O-acetyl-5-methoxytryptophol (aML) synthesis even markedly decreased. Red and blue light did not cause significant changes in MI synthesis. As long as MT synthesis is high (under blue light), there is no increase in FSH content and testes weight is still decreasing. This influence of blue light confirms the putative antigonadotropic properties of MT. The increase of FSH content at week 9 was the first indication that recrudescence had started. At week 19, this recrudescence was also manifested in the increasing testes weight. The synthesis of melatonin (aMT), 5-methoxytryptophol (ML), 5-methoxyindole-3-acetic acid (MA) and aML increased whereas the production of MT decreased. Blue light exposure caused a significantly higher increase of synthesis of ML, MA, aML and, not-significantly, of aMT, whereas red light caused a significantly lower synthesis of MA. It was concluded that MT, a putative antigonadotropic, and aML, a putative counter-antigonadotropic, are probably important pineal compounds that transduce the photoperiodic messages, which cause either gonadal atrophy or recrudescence. The effect of blue light on indole metabolism and the reproductive cycle was more clear than that of red light. From the present results of blue light on indole metabolism, it was suggested that blue light delayed gonadal atrophy and stimulated gonadal growth, compared to red light. An opposite effect of red light was less obvious.

Low temperature in the golden hamster accelerates the gonadal atrophy induced by short photoperiod but does not affect the daily pattern of melatonin secretion.

Male golden hamsters were exposed to short photoperiod at either 20 degrees C or 5 degrees C. After 4 weeks a complete gonadal inhibition was observed in animals kept at 5 degrees C while in animals kept at 20 degrees C such an inhibition was much less. No significant difference in the pattern of pineal and plasma melatonin concentrations was observed between hamsters kept at 20 degrees C and 5 degrees C. If in the golden hamster pineal melatonin secretion is implicated in the transduction of the photoperiodic information, it is probably not implicated in the transduction of thermal information.

The effect of 5-methoxytryptamine on golden hamster gonads is not a consequence of its acetylation into melatonin.

Radioimmunoassay and high performance liquid chromatography were used to determine if the gonadal atrophy induced by late afternoon injections of 5-methoxytryptamine (5-MT) in golden hamsters kept under long photoperiod could be due to the acetylation of this compound into melatonin. An increase in plasma concentrations of melatonin (10-13 nmol/l) was detected 15 min after injection of 130 nmol 5-MT. An injection of 4.3 nmol melatonin generated a similar plasma concentration of melatonin. 5-MT (130 nmol) and melatonin (4.3 nmol) were then injected daily in the late afternoon to golden hamsters kept under long photoperiod. After 8 weeks, 5-MT induced total testicular regression, while melatonin induced partial atrophy only. Thus under these experimental conditions, 5-MT had a physiological activity independent of that of melatonin.

Effects of repeated cycles of fasting-refeeding on brown adipose tissue composition in mice.

Mice fasted for 24 h showed reductions in carcass fat and gonadal fat depots and atrophy of brown adipose tissue (BAT) that was characterized by loss of protein and succinate dehydrogenase. These changes were reversed on 24 h of refeeding. Cycling mice experienced 14 cycles of 1 day of fast followed by 2 days of refeeding, whereas control mice were fed ad libitum. Weight loss during each fast remained constant, and the animals lost and regained in excess of twice their initial weights within 6 wk. However, final weight and carcass and gonadal fat weights were similar to those of animals fed ad libitum. Total food intake was similar between cycling mice and those fed ad libitum suggesting an increase in feeding efficiency. There was no development of resistance to food deprivation since the preceding fasting experience of the animal had no effect on weight and carcass fat loss during a 24- or 48-h fast. Norepinephrine-stimulated oxygen consumption that was reduced in cycling mice was probably the result of a reduction of BAT thermogenic capacity. BAT succinate dehydrogenase content and the concentration of uncoupling protein in isolated mitochondria were significantly reduced. These changes in BAT composition were not observed when the refeeding period of each cycle was increased to 6 days. These results suggest that reduced energy expenditure in BAT may play a role in the conservation of energy during intermittent and frequent bouts of food deprivation.

Influence of photoperiod and gonadal steroids on hibernation in the European hamster.

Torpor was monitored daily in adult male and female European hamsters (Cricetus cricetus) induced to hibernate by exposure to a cold environment (6 degrees C). The effect of photoperiodic manipulations or administration of exogenous gonadal steroids was examined in gonadectomized or intact hamsters. 1. Gonadal regression occurred in all short day, but only in some long day, cold-exposed hamsters. Entry into hibernation was not observed until reproductive regression had occurred. Thus, gonadal atrophy appears to be a necessary precondition for hibernation. 2. Castrated hamsters in the short day cold condition showed a significantly greater incidence of torpor than those in the long day cold condition. Hence, photoperiod affected torpor independently of its effect on the gonadal cycle. 3. Testosterone, when administered via silastic capsules at near physiological levels, completely inhibited torpor in gonadectomized male and female hamsters hibernating in the short day cold condition. 4. In ovariectomized females, torpor was unaffected by progesterone treatment, but partially inhibited by estradiol. A greater inhibition of torpor was observed when estradiol-primed females were administered both estradiol and progesterone simultaneously. Thus, the effect of both hormones may be functionally comparable to that of the single testicular hormone. 5. Estradiol inhibited torpor to a greater extent in intact and ovariectomized female hamsters hibernating in long days than those in short days, suggesting an effect of photoperiod on responsiveness to estradiol. These results indicate an inverse relationship between the gonadal and hibernation cycles, and a probable role for gonadal steroids to influence the timing of the hibernation season. However, non-gonadal factors must also be involved in controlling hibernation, since photoperiod affected the incidence of torpor in gonadectomized animals and because hamsters were able to terminate hibernation in the absence of gonadal hormones.

Preliminary Report of a Comparative Study of Seminiferous Tubular Epithelium from Rats Flown on Cosmos 1887 and SL3

Space flight, with its unique environmental constraints such as immobilization, decreased and increased pressures, and radiation, is known to affect testicular morphology and spermatogenesis. Selye, summarized the manifestations of physiological response to nonspecific stress and he pointed out that atrophy of the gonads always occurred. Reports of data collected from two dogs flown in space for 22 days (Cosmos 110) indicate that there was an increase of 30 to 70% atypical spermatozoa when compared to ground based controls. Seventy-five days after the flight the abnormalities had decreased to the high normal value of 30% and mating of these dogs after this period produced normal offspring, suggesting complete recovery. Effects of immobilization and increased gravity were investigated by spinning rats and mice at 2x g for 8-9 weeks. A decrease in testicular weight was noted in spun animals when compared to controls. Immobilization has been show to cause arrest of spermatogenesis in Macaca meminstrins.

Temporal changes in medial basal hypothalamic catecholamines in male Syrian hamsters exposed to short photoperiod

The gonadal and accessory organ atrophy following transfer of male hamsters from long (LP) to short photoperiod (SP) is preceded by reduced prolactin secretion and involves reductions in hypothalamic LHRH release and catecholamine turnover. These experiments examined the temporal aspects of changes in medial basal hypothalamic/median eminence (MBH/ME) catecholamine turnover rates in male hamsters undergoing SP-induced gonadal atrophy. Hamsters were sacrificed at three, six, nine and twelve weeks of SP exposure. MBH/ME catecholamines and indoleamines were determined by high performance liquid chromatography coupled with electrochemical detection. Reductions in serum prolactin (PRL) levels and increased MBH/ME dopamine (DA) turnover rates were observed at three and six weeks of SP exposure. Both steady state concentrations and turnover rates of norepinephrine (NE) and DA were depressed after nine and twelve weeks of SP exposure, at which time testicular and accessory organ atrophy had occurred. Serotonin (5-HT) and 5-hydroxy-3-indoleacetic acid (5-HIAA) concentrations were insignificantly changed during the period of SP treatment but the 5-HIAA/5-HT ratio was significantly increased after six weeks of SP exposure. It was concluded that increased MBH/ME DA turnover represents an initial, SP-induced neuroendocrine event. This increase in DA turnover probably contributes to the reduced PRL secretion which precedes, and may play a role in the ensuing gonadal and accessory organ atrophy.

The effect of different photoperiods on the methylating capacity of the pineal gland of adult, male golden hamsters, with special reference to 5-methoxyindoles

Testes weight, plasma FSH and LH concentration and pineal methylating capacity were compared in hamsters housed under either long (LD14:10) or short (LD8:16) photoperiods. Hamsters housed for 14 weeks under short photoperiod showed gonadal atrophy, which was complete after 6 weeks. Also plasma FSH and LH concentration showed a marked decline after transfer to short photoperiod. However, after 14 weeks the concentration of FSH and LH as well as testes weight increased again. Under both photoperiods day/night rhythms in plasma FSH and LH concentration were measured. Under both light regimes the concentrations did not show significant differences. Under long as well as short photoperiods in the pineal gland of animals no significant differences were found in the daily synthesis of various MI tested. Only the synthesis of ML was significantly higher in the pineal of hamsters housed under short photoperiod. The function of this higher synthesis of ML remains unknown. Although the maxima of the rhythm for the various MI found under different LD regimes did not differ in magnitude or duration, their location in respect to the onset of darkness was different. It is suggested that this specific location is of more physiological importance than the quantity or duration of synthesis, concentration or release of MI. At the moment the day/night rhythms were determined there were indications that recrudescence of the testes had already started. It is suggested that this recrudescence is responsible for the fact that no differences in the synthesis of MI were found comparing the influence of both photoperiods. After 14 weeks of exposure to short photoperiod, aML synthesis was, in contrast to the synthesis of the other MI, (not significantly) higher under LD8:16. Moreover, opposite results for aMT and aML synthesis during darkness were found. It is suggested that the ratio of synthesis of these compounds is of physiological significance.

Exercise reduces gonadal atrophy caused by short photoperiod or blinding of hamsters

The effect of voluntary exercise upon several reproductive parameters was assessed in male Syrian hamsters. Forty-two animals were caged in five groups and then blinded: Ten housed five per plastic cage; eight housed individually in plastic cages; six housed individually in plastic cages with 15 cm exercise wheels in the cage; eight housed in Wahmann steel activity cages with 36 cm wheels locked to prevent rotation; ten housed in functional Wahmann running wheel cages. At 16 weeks after blinding, animals with access to functional running wheels had significantly larger testes (3.7±1.0 g) than those with no wheels or locked wheels (1.86±0.6 g; mean±SD; p<0.001). These results suggested that voluntary exercise reduces testicular atrophy caused by blinding. A second experiment was run in which the animals were subjected to a short photoperiod (LD 6:18) for 12 weeks instead of blinding. Similar results were obtained except that access to the small exercise wheels did not affect testicular atrophy: Mean testicular mass of animals in individual cages=0.79±0.3 g, small wheels=0.74±0.4 g, functional Wahmann wheels, 2.56±1.0 g, locked Wahmann wheels 0.52±0.1 g ( p<0.01).

Daily and seasonal rhythmicity in the methylation of pineal indolic compounds in adult male golden hamsters, kept under natural conditions.

Seasonal rhythmicity in the reproductive cycle was demonstrated in golden hamsters exposed to natural conditions. Testes regress in weight and function from October up to April. Reproductive functional testes are found in June. Although less marked, body weight also shows seasonal variations: a retarded growth in winter and early spring. In the pineal gland of these animals diurnal and seasonal rhythmicity was found in the synthesis of various MI. It has been concluded that rhythms in the pineal of animals kept under artificial conditions are often more pronounced as compared to those in hamsters kept under natural conditions. Melatonin (aMT) synthesis was observed during the day as well as during the night. A certain resemblance in patterns of day/night rhythms as to aMT and 5-methoxytryptamine (MT) production was reported suggesting a physiological role of MT. To facilitate the discussion on seasonal rhythmicity the average synthesis per day of the 5-methoxyindoles (MI) was calculated. During the period of gonadal regression in fall and early winter, MT and aMT, which are both generally accepted as pineal antigonadotropins, showed opposite patterns in rhythms of mean synthesis; MT decreased but aMT increased from October up to December. It was suggested that under natural conditions MT may induce and aMT maintain gonadal atrophy. Furthermore, also other MI showed relatively high amounts of production, at least in November. The period of recrudescence was characterized by a high synthesis of 5-methoxytryptophan (MW), 5-methoxytryptophol (ML) and O-acetyl-5-methoxytryptophol (aML). This confirms an earlier suggestion that aML can be considered a counter-antigonadotropic substance of the hamster pineal gland. Therefore it was concluded that, apart from MT and aMT, also other MI may be of physiological importance in the regulation of gonadal atrophy.

Effects of photoperiod and hCG on the regulation of testicular LH/hCG receptors in Syrian hamsters (Mesocricetus auratus).

The regulation of testicular LH/hCG receptors was studied in Syrian (golden) hamsters with testicular atrophy induced by exposure to short photoperiod (5L:19D) and in gonadally active hamsters kept in a long photoperiod (14L:10D). By 24 h after injection of hCG, long-photoperiod hamsters showed a dose-related decrease in the number of testicular LH/hCG receptors. At 48 and 72 h, there was a recovery from this 'down-regulation'. The recovery was much faster than has been reported for the rat and mouse, and it resulted in elevation of testicular LH/hCG receptor concentrations above basal values. Hamsters with short photoperiod-induced testicular atrophy showed an increase in testicular LH/hCG receptors after injection of hCG, except for animals injected with a very high dose. The hCG-induced increase in testicular LH/hCG binding in these animals was associated with reappearance of testosterone responses to subsequent hCG stimulation. Response of testicular LH/hCG receptors to hCG in prepubertal hamsters resembled that measured in animals with short photoperiod-induced gonadal atrophy.

Effects of inhibitory and stimulatory photoperiods and sexual maturation on the ability of hamster testes to respond to hCG in vitro.

The decrease in gonadal weight produced in adult golden hamsters by exposure to short photoperiods was accompanied by a marked reduction in the ability of the testes to produce testosterone from endogenous precursors in vitro, both without and with hCG stimulation. These changes were significant after 4-7 weeks in short photoperiod (5L: 19D) and were even more pronounced after 17-20 weeks. Production of testosterone in vitro by testes of immature hamsters was comparable to values obtained in adult animals with short photoperiod-induced gonadal atrophy. Delay of sexual maturation induced by daily injections of bromocriptine was accompanied by a further decrease in testicular testosterone production in vitro. Exposure of gonadally-regressed adult hamsters to a long, stimulatory photoperiod (14L: 10D) produced a rapid and marked increase in testicular testosterone production, which was coincident with the previously demonstrated increase in serum gonadotrophin levels after 1-5 days of photostimulation. Furthermore, testosterone production in vitro by regressed testes of animals exposed to short photoperiod was increased significantly by one large dose of hCG administered 26 h before killing the animals. It is concluded that the suppressive effects of short photoperiods on the ability of the hamster testis to produce testosterone and to respond to hCG stimulation are due to reductions in endogenous LH, FSH and prolactin release, with a consequent loss of testicular LH/hCG receptors and decreased activity of enzymes involved in the biosynthesis of testosterone.

The effect of reduced neopterin on the synthesis of several methylated indoles in the pineal gland of adult male golden hamsters, kept under standardized conditions.

In the present study the effect was tested of reduced neopterin (RN) on the methylating capacity of the pineal gland of adult, male golden hamsters, housed under standardized conditions throughout the year. An effect of RN on the synthesis of a number of methylated compounds was, indeed, demonstrated. It is concluded that RN not only influences the indole metabolism by being the cofactor of tryptophan-hydroxylase, but that it might be involved in the regulation of other enzymes as well. Incubation with RN was most effective at the end of the light period. As this is also the time at which melatonin (aMT) injections cause gonadal atrophy in hamsters, kept under long photoperiod, this time of the day may be very important for aMT synthesis. A season-bound influence of RN was also demonstrated. The effect of RN was stimulatory in September, November and January for 5-methoxy-tryptamine (MT) and in November for 5-methoxytryptophan (MW) synthesis, but inhibitory in July. Furthermore, the effect of RN was stimulating for 5-methoxyindole-3-acetic acid (MA) and aMT in September, while the influence in the other months tested was absent or slightly inhibiting. These results suggest that the influence of RN in the pineal may be regulatory to various enzymes of the indole metabolism.

An ovarian regression syndrome in the platyfish, Xiphophorus maculatus.

The highly inbred Coatzacoalcos (Cp) strain of the platyfish, Xiphophorus maculatus, was noted for a high percentage of infertile females (XX). The ovaries of approximately one-quarter of all females regress. The time of gonadal atrophy varied from before sexual maturation up to 11 months of age. The gonadotropic zone of the pituitary was hypertrophied in regressed females. Transplants of immature testes and ovarian tissue into the caudal musculature of regressed females and the subsequent maturation of the grafts demonstrated that the ovarian degeneration was not due to pituitary or hypothalamic malfunction or an autoimmune disease. The cause of the gonadal degeneration was apparently localized to the ovary itself. This phenomenon was never observed in males (XY). Regressed ovaries fell into two categories, designated types I and II, with all being characterized by the presence of ductlike structures which resembled male efferent ducts, lined by Sertoli cells. Type I ovaries bore a marked similarity to certain mammalian dysgenetic gonads, while type II ovaries contained many proliferating germ cells and could be compared to the human neoplasm termed gonadoblastoma. It is suggested that the physiological lesion responsible for the ovarian regression syndrome involves the processes that control the determination and differentiation of the germ cells similar to those found in human 46,XY gonadal dysgenesis.

The Reproductive Effects Assessment Group's report on the mutagenicity of 1,3-butadiene and its reactive metabolites.

A major data gap for assessing heritable risk from exposure to 1,3-butadiene is the lack of mammalian mutagenicity data. The data base on the mutagenic potential of 1,3-butadiene is limited to three bacterial studies from the same laboratory. Two of these studies were positive only in the presence of liver S9 mix from chemically pretreated animals. In vitro data suggest that 1,3-butadiene is metabolized to two epoxide intermediates. 3,4-Epoxybutene, one potential reactive metabolite of 1,3-butadiene, is a monofunctional alkylating agent and is a direct-acting mutagen in bacteria. In addition, unpublished data suggest that 3,4-epoxy-butene induces DNA damage and chromosomal aberrations in mice. Another potential reactive metabolite, 1,2:3,4-diepoxybutane, is a bifunctional alkylating agent and is mutagenic in a wide variety of organisms (bacteria, fungi, and the germ cells of Drosophila). This metabolite also induces DNA damage in mice and in cultured hamster cells, is clastogenic in fungi and cultured rat cells, and produces chromosome damage/breakage in Drosophila germ cells. These data, when combined with evidence that 1,3-butadiene is carcinogenic in rodent gonadal tissues and is associated with gonadal atrophy in mice, constitute suggestive evidence that 1,3-butadiene may be a human germ cell mutagen. However, because the mutagenicity of 1,3-butadiene has been studied only in bacteria, studies in mammalian test systems are needed to further characterize the mutagenic potential of 1,3-butadiene.

Melatonin does not alter human serum gondotropin and testosterone levels, but it increases prolactin levels

Administration of the pineal hormone melatonin (MEL) lowers serum gonadotropin (GN) levels, delays sexual maturation and elicits gonadal atrophy in rodents. In humans an antigonadotropic effect of the pineal has been sought for many years. Recently we reported higher nocturnal serum MEL levels in prepubertal children than in young adults. Now we have examined the immediate effects of exogenous MEL on basal levels of various hormones. After giving informed consent 5 healthy, male adolescents received 80 mg oral MEL at 11:00; 3 volunteers received the same dosis at 11:00,12:00 and 13:00. Serum concentrations of MEL, GN, testosterone (T) and prolactin (PRL) were determined at 30-min. intervals several hours prior to, during, and after MEL administration. Though serum MEL concentrations increased at least 1000 times above basal levels GN and T were not altered. PRL rose from 4.6±0.7 (x±SEM) to 7.6±0.9 ng/ml (p<0.005) after MEL application. To examine the effect of the pineal hormone on the pulsatile secretion patterns of GN and PRL, in 2 adolescents sera were taken at 10-min. intervals for 6 hours before and after MEL treatment. The pulstile secretion pattern of GN was not altered by MEL; again, PRL levels were higher after MEL than before. Thus, a single dosis of MEL does not affect serum GN levels in humans, but it increases PRL serum concentrations.

Differential effects of cryptorchidism and short photoperiod on testicular prolactin and LH/human chorionic gonadotrophin receptors in the golden hamster.

Gonadal atrophy induced by short photoperiods in male golden hamsters is accompanied by a decrease in the total content of testicular prolactin and LH/human chorionic gonadotrophin (LH/hCG) receptors and a concomitant rise in the concentrations of LH receptors. Atrophic testes are typically abdominal. In this study, we have compared the effects of experimentally induced cryptorchidism and the effects of a short photoperiod on testicular prolactin and LH/hCG receptors. Cryptorchidism produced the expected decrease in testicular weight and an increase in plasma FSH concentrations, without altering plasma concentrations of LH or prolactin and with a relatively small decrease in plasma testosterone. It also produced an increase in the concentration of prolactin and LH/hCG receptors without significant changes in their total content. Exposure to a short photoperiod decreased weights of testes and seminal vesicles and plasma levels of prolactin and testosterone, with no significant effects on plasma gonadotrophin levels. Short photoperiod also increased the concentration of LH/hCG receptors but, in contrast to the effects of cryptorchidism, it produced a precipitous decline in the total content of testicular receptors for both prolactin and LH/hCG. We conclude that changes in prolactin and hCG binding measured in membrane preparations from decapsulated testes of hamsters exposed to a short photoperiod cannot be explained by the abdominal position of the gonads, abnormalities of Sertoli cell function or changes in the relative proportion of Leydig cells in the atrophic testes.

An immunocytochemical study of the luteinizing hormone-releasing hormone (LHRH) system in the white-footed mouse: effect of blinding and melatonin.

Previous studies have provided evidence that pineal-mediated gonadal atrophy involves the luteinizing hormone-releasing hormone (LHRH) system in some rodents. The purpose of the present study was to visualize the LHRH system in the brain of the white-footed mouse by immunocytochemical methods and to assess the influence of blinding or melatonin on the LHRH immunostaining characteristics of the median eminence. Six intact adult female mice and six adult males (two intact, two blinded, and two with subcutaneous melatonin-beeswax implants) treated for 6 wk were sacrificed by perfusion of fixative, and their brains were removed, cut into 60-micron sections and stained for LHRH by the peroxidase-antiperoxidase (PAP) method. Since the tissues were batch-processed in separate wells in a common chamber, semiquantitive comparisons may be made between similar sections from animals subjected to different treatments. The testes were also collected and prepared for microscopic examination. The distribution of LHRH-stained cell bodies and fibers was found to be essentially the same as has been described in other rodents, i.e., predominantly confined to the preoptic area and hypothalamus. The perikarya appear as unipolar and bipolar fusiform cells with "beaded fiber" type processes. In sections that included the median eminence of the blinded and melatonin-treated males, the degree of immunopositive staining appears to be greater than in the median eminence of untreated mice. The histological appearance of the testes from the treated animals revealed a profound inhibition of gametogenesis. These observations support the suggestion that pineal-mediated gonadal atrophy is the result of an inhibition of LHRH release from the median eminence.

Differential Responsiveness of the Reproductive System of Blind or Melatonin‐Treated Male Hamsters to Injections of Gonadotrophin‐Releasing Hormone (GnRH) and/or Prolactin

The combination of pituitary grafts and daily injections of gonadotrophin-releasing hormone (GnRH) completely prevents gonadal atrophy 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 micrograms). In each experiment the hamsters were BL and/or treated with hormones for 10 wk. Either GnRH (8 micrograms) or PRL (5 micrograms) per d partially prevented gonadal atrophy in BL hamsters. However, increasing doses of GnRH plus PRL were 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.