Biomedical subjects

G R Buzzell

Publications and source records attributed to G R Buzzell.

At least 37 records · Page 2Linked to original sources

PubMed1991

Effects of prepubertal manipulation with androgens on the development of sexual differences in the harderian glands of Syrian hamsters.

The onset of sexual differences in the metabolism of porphyrins and melatonin in the Harderian glands of Syrian hamsters was studied. Three weeks after birth, the porphyrin concentrations were already higher in glands of females than in those of males. Castration of 22-day-old male hamsters led to an increase in Harderian porphyrin concentrations, although the levels of intact females were not reached. The administration of testosterone to 22-day-old female hamsters resulted in a marked decrease in porphyrin concentrations. Study of the development of sexual differences in the enzymes involved in melatonin synthesis, N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT) indicated that not all the sexual differences observed in these glands begin at the same time. Thus, while differences in NAT activity were detected after the age of 3 weeks, male-female differences in HIOMT activity were only observed after 7 weeks. Castration of prepubertal male hamsters lowered NAT but not HIOMT activities. The administration of testosterone to prepubertal female hamsters led to male activity levels in both enzymes. Although circulating androgens seem to have a crucial role in maintaining sexual differences, other hormones including those from the pituitary and thyroid glands are probably also important for generating these sexual differences.

Acetylserotonin O-Methyltransferase↗

PubMed1990

In vivo administration of isoproterenol or forskolin during the light phase induces increases in the melatonin content of the Syrian hamster pineal gland without a rise in N-acetyltransferase activity.

In vivo melatonin production was stimulated during the daytime in pineal glands of female Syrian hamsters following the administration of several injections of either isoproterenol, a beta-receptor agonist, or forskolin, an adenylate cyclase stimulator. The large increase in melatonin following either isoproterenol or forskolin administration was not accompanied by significant changes in N-acetyltransferase (NAT) activity. The results suggest that the Syrian hamster pineal gland, as in other species, responds by producing melatonin during the light phase if the stimulus is adjusted to its particular and specific regulatory mechanisms, i.e., if beta-adrenergic stimulation is continued for 4-8 h. The lack of a commensurate increase in NAT activity raises the question of the need of maximal enzymatic activity for a significant rise in melatonin production in the Syrian hamster pineal gland.

Acetyltransferases↗

PubMed1990

Androgenic control of N-acetyltransferase activity in the harderian glands of the Syrian hamster is mediated by 5 alpha-dihydrotestosterone.

N-acetyltransferase (NAT) activity in the Harderian glands of intact and gonadectomized male and female Syrian hamsters was evaluated. The exogenous administration of 5 alpha-dihydrotestosterone (DHT) to castrated males and intact females produced an increase in NAT values, which reached the values present in the glands of intact males. The administration of a 5 alpha-reductase inhibitor to intact males led to a decrease in NAT activity, suggesting that testosterone is converted in DHT within the glands. It is concluded that NAT activity in the Syrian hamster Harderian glands is under androgenic control, the active steroid being DHT.

5-alpha Reductase Inhibitors↗

PubMed1990

Further studies on the regulation of the Harderian glands of golden hamsters by the thyroid gland.

Long-term increased or decreased circulating levels of thyroid hormones significantly modify porphyrin concentrations and morphology in the Harderian glands of male and female hamsters. Administration of T3 reduced porphyrin concentrations in females; this treatment or decreasing thyroid hormone levels with KClO4 suppressed the post-castration rise of porphyrins in males. Hypophysectomy led to increased porphyrins in the Harderian glands of males; this rise was suppressed in hypophysectomized males by T3 or T4. In females, hypophysectomy reduced porphyrins which were further reduced by daily administration of T3 or T4. These modifications in the normal females were identical in castrated males. Mitotic activity in the Harderian glands of females was stimulated by KClO4 and by hypophysectomy with or without exogenous T3. In males, castration increased mitotic activity which was suppressed by T3 and exacerbated by KClO4. Increased mitotic activity seemingly follows loss of tissue mass. The data show that thyroid hormones act directly on the Harderian glands rather than indirectly through modification of TSH synthesis/release. Female "type" glands in males are a consequence of loss of gonadal androgens by castration, or by suppression or loss of thyroid hormones by hypophysectomy or by treatment with KClO4. However, male "type" glands in females are the result of androgen treatment, and/or increased levels of thyroid hormones via reduced ambient temperatures or of photic input. We conclude that regulation of the Harderian gland appears to be different in the two sexes.

Analysis of Variance↗

PubMed1990

Melatonin and porphyrin in the harderian glands of the Syrian hamster: circadian patterns and response to autumnal conditions.

1. Adult male Syrian hamsters were killed at nine intervals during a 24 hr period in the autumn, after 2 months either indoors in controlled conditions or in natural outdoor conditions. 2. Harderian glands were taken for determination of N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT) activities and melatonin and porphyrin concentrations. 3. Mean 24 hr Harderian NAT and melatonin values were lower outside than inside. 4. Twenty-four hour melatonin rhythms were detected with similar daytime (afternoon) acrophases in both environmental conditions. 5. An NAT rhythm was seen only in animals kept inside, with a circadian maximum in the late dark phase. 6. Mean 24 hr HIOMT activity was slightly higher outdoors than indoors, and 24 hr rhythms were not detected in either condition. 7. Mean porphyrin concentrations were higher outdoors, with 24 hr rhythms detected in both conditions and a significantly earlier nocturnal circadian maximum outdoors.

Acetylserotonin O-Methyltransferase↗

PubMed1990

Pineal lysosomal enzyme circadian rhythms in male hamsters exposed to natural decreasing photoperiod and temperature conditions.

Circadian rhythms in acid phosphatase (ACP), hexosaminidase (HEX) and beta-glucuronidase (RON) activity were studied in the pineal glands of adult male Syrian hamsters exposed to control (20 +/- 2 degrees C and 14:10 LD) conditions or to naturally decreasing autumn photoperiod and temperature conditions (outside) for 8 weeks. Testes and testosterone levels (p less than 0.001 in both instances) were severely depressed in animals exposed to natural environmental conditions illustrating that the treatment period was of sufficient length to produce pineal-mediated gonadal atrophy. Significant rhythms were found in all enzymes in the pineal glands of control and outside animals with the exception of HEX activity in the control animals. Significant acrophase differences in outside vs. control animals were noted in ACP (7.9 hr earlier, p less than 0.001) and RON (9.8 hr later, p less than 0.001). A significant drop in RON and HEX activity (p less than 0.01 in both instances) was noted in association with the acute lights exposure in the morning to which control animals were exposed. The around-the-clock mean value of each enzyme was significantly lower in outside vs. control hamsters. These results demonstrate that environmental changes which provoke the pineal-mediated depression in gonadal activity also alter the activity of and shift the circadian rhythmicity of lysosomal enzymes in the pineal itself.

Acid Phosphatase↗

PubMed1990

Effects of short-day photoperiods and of N-(2,4-dinitrophenyl)-5-methoxytryptamine, a putative melatonin antagonist, on melatonin synthesis in the Harderian gland of the Syrian hamster, Mesocricetus auratus.

The Harderian glands of Syrian hamsters contain melatonin and the enzymes N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT) which synthesize melatonin from serotonin. Because the Harderian glands share this metabolic pathway with the pineal gland, we examined the effects of short-day photoperiods, which stimulate pineal-mediated gonadal regression, and N-(2,4-dinitrophenyl)-5-methoxytryptamine (ML-23), which has been described as a melatonin antagonist, on melatonin synthesis in the Harderian glands of the hamster. Harderian glands of male hamsters kept in short days had reduced NAT activity and melatonin concentration, but HIOMT activity was unchanged from that of long-day controls. In males kept in short days, ML-23 restored melatonin concentrations to levels seen in long days but did not affect the short-day induced reduction in NAT activity. ML-23 had no effect upon NAT or HIOMT activity or melatonin concentration in male hamsters kept on long days. Harderian glands of female hamsters kept on short days had reduced melatonin concentrations, but NAT and HIOMT activities similar to those of long-day controls. ML-23 had no effect on Harderian NAT or HIOMT activities or melatonin concentration in females kept in short days. However, in females kept in long days, ML-23 treatment led to increased NAT activity and decreased melatonin concentrations. We conclude from these results that short-day photoperiods alter some aspects of melatonin synthesis in hamster Harderian glands and that these effects differ in males and females. ML-23 does not usually prevent the effects of short days on Harderian melatonin synthesis, suggesting that it is not a melatonin antagonist in the Syrian hamster.

5-Methoxytryptamine↗

PubMed1990

N-acetyltransferase activity in the Harderian glands of the Syrian hamster, Mesocricetus auratus, is regulated by androgens and by hormones of the pituitary-thyroid axis.

This study tested the hypothesis that activity of the enzyme N-acetyltransferase (NAT) in the Harderian gland of the Syrian hamster is regulated both by androgens and by hormones of the pituitary-thyroid axis. To test the effects of castration and hypothyroidism, intact or castrated male hamsters were given either tap water or methimazole in their drinking water for 3 weeks. Methimazole suppresses iodination of thyroglobulin, thereby decreasing circulating levels of thyroid hormones and increasing TSH levels. Hypothyroidism or castration caused elevated or depressed Harderian gland NAT activities respectively, compared with euthyroid controls. When castration and hypothyroidism were combined, the animals exhibited high NAT activity compared with castrated euthyroid males. To test the effects of castration and hyperthyroidism, male hamsters were given daily injections of thyroxine (T4) or diluent and were either castrated or left intact for 4 weeks. Intact animals given T4 had depressed Harderian NAT activity; serum thyroid hormone levels were elevated and TSH levels were depressed compared with those of intact controls. Castrated animals had depressed NAT activity below that of intact controls; serum thyroid hormone levels were normal but TSH levels were depressed. Castrated animals given T4 injections had NAT activity similar to that of euthyroid castrated hamsters; thyroid hormone levels were elevated but TSH levels were similar to those seen in euthyroid castrated hamsters. In another experiment, both T4 and tri-iodothyronine (T3) were equally effective in decreasing NAT activity in intact males. To determine the effects of the removal of pituitary influences, male hamsters were hypophysectomized. NAT activity in the Harderian glands of these animals was reduced compared with intact controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgens↗

PubMed1989

Pineal lysosomal enzymes in the Syrian hamster: circadian rhythm and effects of castration or short photoperiod treatment.

A circadian rhythm in acid phosphatase and hexosaminidase was found in adult male hamsters exposed to a long photoperiod (14:10 h light/dark [LD]; lights on 06.00 h) and killed at 08.00, 14.00, 20.00, 02.00, 04.00, 05.50 and 0.615 h. Hexosaminidase and beta-glucuronidase activity at 02.00, 04.00 and 05.50 h (values pooled for these times before lights on) were significantly elevated compared to enzyme activity at 06.15 and 08.00 h (pooled values after lights on), suggesting a fall in activity associated with lights on. Hypogonadism was induced in female Syrian hamsters by exposure to a short photoperiod (10:14 h LD) until a majority of them were vaginally acyclic. Pineal lysosomal enzyme activities (acid phosphatase, beta-glucuronidase, hexosaminidase, alpha-arabinosidase and beta-galactosidase) were significantly elevated in short photoperiod-exposed animals compared to animals in 14:10 LD, when measured near the middle of the light phase. In the third experiment, castrated animals were used to determine if lowered androgen levels might also affect pineal lysosomal enzyme activity. The results indicated that light phase beta-glucuronidase, hexosaminidase and beta-glucosidase activities were lower in castrated males compared to their intact controls. In summary, these results demonstrate that (1) lysosomal enzyme activity is present in the Syrian hamster pineal, (2) changes can be observed which suggest involvement of this activity in pineal function and, (3) a circadian rhythm in enzyme activity is present with peak activity occurring during the night. In the short photoperiod and castration experiments, the changes in lysosomal enzyme activity could reflect either a hormonal manipulation or a change in circadian regulation of enzyme activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid Phosphatase↗

PubMed1989

Bromocriptine prevents the castration-induced rise in porphyrin concentration in the harderian glands of the male Syrian hamster, Mesocricetus auratus.

The Harderian glands in Syrian hamsters exhibit a striking sexual dimorphism. Male Harderian glands show two cell types and low levels of porphyrins and melatonin. Of the enzymes involved in the synthesis of melatonin, N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT) show high and low activity levels, respectively. Female Harderian glands show but one cell type and have high porphyrin and melatonin levels, low NAT activity, and high HIOMT activity. In castrated males, the Harderian glands exhibit a female pattern of morphology, porphyrin levels, and indoleamine metabolism. In an attempt to determine whether prolactin in involved in this sexually dimorphic response of the Harderian glands, intact and castrated male and intact female hamsters were injected daily with 500 micrograms of bromocriptine, a dopamine agonist. Bromocriptine led to reduced serum prolactin levels in all groups. It had no apparent effect on the Harderian glands of intact males. In contrast, in castrated males bromocriptine prevented the postcastrational rise in porphyrin levels but had no effect on NAT or HIOMT activities. In females, bromocriptine treatment had no effect on porphyrin concentrations or HIOMT activity; it led to a statistically significant increase in NAT activity. We propose that testosterone inhibits Harderian porphyrin synthesis while dopamine or prolactin stimulates it.

Animals↗

PubMed1989

Characterization of beta-adrenoceptors in the Syrian hamster Harderian gland: sexual differences and effects of either castration or superior cervical ganglionectomy.

Scatchard analysis of saturation isotherms of [125I]-iodopindolol was used to characterize beta-adrenoceptor density (Bmax) and affinity constant (Kd) in female and male hamster Harderian glands. Single-point experiments were also completed in intact females, intact males, and castrated or superior cervical ganglionectomized males. Scatchard analysis described a single population of binding sites with a Bmax of 292.2 +/- 45.1 fmol/mg protein (X +/- SEM, n = 6) in females and 18.2 +/- 3.0 fmol/mg protein (n = 6, P less than .001) in males. The affinity also varied significantly (P less than .05) with a Kd of 1.08 +/- 0.18 versus 0.26 + 0.05 nM (n = 6) in the Harderian gland of females and males, respectively. Single-point [125I]-IPIN (400 pM) binding values in females were 67.3 +/- 4.0, in intact males were 12.8 +/- 3.2, and in castrated males were 31.2 +/- 4.2 fmol/mg protein (n = 7-9). Superior cervical ganglionectomy induced no significant changes in receptor binding. The results indicate pronounced sexual differences in the density and affinity of beta-adrenoceptors in the hamster Harderian gland, which may be sex hormone dependent.

Animals↗

PubMed1989

Heme precursor 5-aminolevulinic acid alters brain tryptophan and serotonin levels without changing pineal serotonin and melatonin concentrations.

The daytime administration of the heme precursor 5-aminolevulinate (5-ALA) has been shown to reduce brain tryptophan and serotonin levels owing to saturation of liver tryptophan pyrrolase. Saturation of this enzyme with heme results in enhanced activity, leading to increased catabolism of tryptophan and thus making less tryptophan available to the brain. Tryptophan is also the precursor of melatonin, a primary secretory product of the pineal gland. Reduced melatonin levels, which could be a consequence of altered tryptophan metabolism, have been associated with depressive disorders in humans. In view of this, in the present study we examined the effects of 5-ALA administration on forebrain tryptophan and serotonin levels as well as pineal serotonin, melatonin, and the pineal melatonin-forming enzymes N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT). 5-ALA induced a reduction in forebrain tryptophan and serotonin levels during the light phase and caused the opposite effect in the dark phase. Allopurinol, an inhibitor of hepatic tryptophan pyrrolase activity, prevented the reduction in the indole levels induced by 5-ALA. Although 5-ALA induced these changes in the forebrain, it did not alter either daytime or nighttime pineal NAT, HIMOT, serotonin, or melatonin levels. It appears that high serotonin levels and melatonin production in the pineal are conserved even in the face of low circulating tryptophan levels, changes which alter brain tryptophan and serotonin concentrations.

Animals↗

PubMed1989

Effects of inhibition of thyroid function and of cold on melatonin synthesis and porphyrin content in the Harderian glands of male Syrian hamsters, Mesocricetus auratus.

1. Indole metabolism and porphyrin content of the Harderian glands of the male Syrian hamster were measured as functions of drug-induced hypothyroidism and exposure to cold conditions. 2. Harderian gland N-acetyltransferase (NAT) activity was reduced from control levels by hypothyroidism induced by methimazole; exposure to cold had no effect on NAT activity. 3. Immunoreactive melatonin in the Harderian glands was unaffected by the state of thyroid secretion. However, immunoreactive melatonin content declined after 180 and 270 min, at 4 degrees C, suggesting that Harderian gland melatonin may be involved in thermoregulation. 4. Porphyrin content of the Harderian glands was not affected by either thyroid secretion or cold.

Animals↗

PubMed1989

Architecture of the dorsal and ventral lobes of the prostate of the Syrian hamster, Mesocricetus auratus, after regrowth from short day-induced regression.

The structures of the dorsal and ventral lobes of the prostate of 4 groups of Syrian hamsters were studied by a stereological approach. Groups studied were young hamsters (kept in long-day photoperiods for 4 weeks) in their first breeding season, older hamsters (kept in short-day photoperiods for 24 weeks so that their prostates had regressed and regrown) in their second breeding season, and two groups of older hamsters in an extended first breeding season (either because they were kept in long days for 24 weeks or because they were pinealectomized before being put into short-day photoperiods for 24 weeks). There were very few differences between groups, but generally dorsal prostates of older hamsters in their second breeding season closely resembled those of young hamsters in their first breeding season. More differences were noted between either of these two groups and older hamsters in an extended first breeding season than between these two groups. The differences noted generally involved increases in the amount of smooth muscle in the walls of secretory tubules in the dorsal prostates of hamsters in an extended first breeding season. This may be associated with the fact that these glands had not regressed and regrown. Ventral prostates were very similar in all 4 groups, which may reflect the fact that they normally regress very little in short days.

Animals↗

PubMed1989

Swimming-induced suppression of rat pineal melatonin is prevented by pretreatment with calcium channel blockers.

Young adult male rats were treated with isoproterenol during the day to induce high levels of pineal N-acetyltransferase (NAT) activity and melatonin. Roughly 2 hr later when pineal NAT activity and melatonin levels were elevated, animals were given either an injection of a calcium channel blocker, i.e., either nifedipine or verapamil, or diluent. The rats were then forced to swim for 10 min in room temperature (22 degrees C) water. Fifteen minutes after swimming onset, pineal glands were collected for measurement of NAT activity and melatonin. Swimming caused a dramatic reduction in pineal melatonin content without influencing NAT activity. Nifedipine substantially and verapamil completely blocked the drop in pineal melatonin levels due to swimming without influencing NAT activity. The results suggest that calcium may be somehow directly or indirectly involved in melatonin release from the rat pineal gland.

Acetyltransferases↗

PubMed1989

5 alpha-dihydrotestosterone administration converts indolamine metabolism and porphyrin content of the female Syrian hamster Harderian gland to the male type.

The effects of ovariectomy and exogenous androgen administration on the indole and porphyrin metabolism of Syrian hamster Harderian glands were studied. Ovariectomy alone had no effect on any of the parameters analyzed. The administration of either testosterone or 5 alpha-dihydrotestosterone increased the activity of N-acetyltransferase in the Harderian glands. However, androgen treatment failed to change the activity of hydroxyindole-O-methyltransferase. Melatonin content of the glands dropped 20 days after treatment with testosterone and 10 days after the administration of 5 alpha-dihydrotestosterone. The porphyrin content of the Harderian glands was dramatically depressed after the administration of either androgen. It is concluded that the Harderian glands of Syrian hamsters are under an androgenic control involving 5 alpha-dihydrotestosterone.

Acetylserotonin O-Methyltransferase↗

PubMed1988

Fine structure of the ventral and dorsal lobes of the prostate in the young adult Syrian hamster, Mesocricetus auratus.

The normal ventral and dorsal prostatic lobes of the young adult Syrian hamster were examined at the light and electron microscopic levels. Each lobe is composed of branched tubular secretory units separated from each other by loose interacinar connective tissue and draining into the urethra. The lumen of each acinus is lined by a simple epithelium composed of columnar secretory cells with occasional small basal cells. The epithelial layer, with the thin underlying lamina propria, forms a mucosa that is often highly folded. The whole acinus is bounded by a thick muscular stroma. In each of the ventral lobes, there are three main ducts, each one formed of tubular branched tributary secretory units. The walls of the secretory acini are moderately folded. Microvilli dominate the lumenal surface of the secretory epithelial cells. The Golgi complex is very extensive and shows dilated cisternae and secretory vesicles and vacuoles of various sizes. Membrane-bounded secretory granules populate the Golgi and apical areas and are released into the acinar lumen by exocytosis. The rough endoplasmic reticulum is dispersed throughout the cytoplasm, except in the region of the Golgi apparatus. In each of the dorsal lobes, there are several main tubular ducts that open into the urethra. Both proximal (ductal) and distal portions of the glandular tree are secretory in nature. Microvilli and cytoplasmic bulges and blebs dominate the lumenal surface of the secretory cells. The cells are also characterized by highly dilated cisternae of rough endoplasmic reticulum. The secretory cells show heterogeneity in the degree of dilation and distribution of rough endoplasmic reticulum, and this heterogeneity may reflect location in the glandular tree.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Studies on the effects of the pineal hormone melatonin on an androgen-insensitive rat prostatic adenocarcinoma, the Dunning R 3327 HIF tumor.

The effects of the pineal indole melatonin on a transplantable androgen-insensitive fast-growing rat prostatic adenocarcinoma, the Dunning R 3327 HIF tumor, were examined. Afternoon injections of melatonin given to intact male rats enhanced tumor growth, while leading to a reduction in the weights of gonads and dorsal and ventral prostates. In anosmic hosts, this treatment had no effect on tumor growth or reproductive organ size. In castrated anosmic hosts, melatonin injections led to reductions in the growth of tumors, when compared with those in castrated hosts. Continuously available melatonin, in beeswax pellets, had no effect on growth of these tumors. These results are discussed in relation to the anticancer effects of melatonin and the effects of tumors on endogenous melatonin rhythms.

Adenocarcinoma↗