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Biomedical subjects

A Bartke

Publications and source records attributed to A Bartke.

At least 109 records · Page 6Linked to original sources
PubMed1995

Ethanol and nicotine consumption and preference in transgenic mice overexpressing the bovine growth hormone gene.

Transgenic mice overexpressing the phosphoenolpyruvate carboxykinase/bovine growth hormone (PEPCK/bGH) hybrid gene and normal (nontransgenic) littermate controls (10 males + 10 females/group) were given access to tapwater and an ascending series of concentrations of ethanol (1.0-22.0%), then a similar ascending series of concentrations of nicotine (1.0-40.0 micrograms/ml), in a two-bottle choice test. Male transgenic mice consumed more and exhibited greater preferences for ethanol and nicotine than control males; transgenic females consumed less and showed lower preferences for ethanol, but not nicotine, than control females. These results suggest that chronic exposure to high levels of bGH may modulate the rewarding effects of ethanol and nicotine in mice in a gender-specific fashion.

Alcohol Drinking↗
PubMed1995

Ethanol, nicotine, amphetamine, and aspartame consumption and preferences in C57BL/6 and DBA/2 mice.

Using a two-bottle choice paradigm, adult C57BL/6 and DBA/2 mice (11 males an 10 females per strain) were given access to tapwater and an ascending series of concentrations of ethanol, nicotine, amphetamine, and th artificial sweetener, aspartame. The C57 mice consumed more ethanol, nicotine, and amphetamine, and showed greater preferences for these substances, than did the DBA/2 mice. In contrast, DBAs consumed more and showed greater preference for aspartame than C57s. However, measures of drug and aspartame consumption and preference were moderately intercorrelated when the effects of gender and strain were controlled for. This pattern of results suggests that factors modulating differences between C57BL/6 and DBA/2 mice in ethanol consumption and preference also modulate differences in consumption of nicotine and amphetamine.

Administration, Oral↗
PubMed1995

Developmental changes of tachykinins in the hypothalamus and anterior pituitary of female Siberian hamsters from prepuberty to adulthood.

The developmental changes of hypothalamic and anterior pituitary tachykinin concentrations were studied in female Siberian hamsters kept either under short (SD) or long (LD) daily photoperiods. The animals were killed between 15 and 70 days of age. Hypothalamic NKA sharply increased starting at 15 days up to 50 days in LD animals, and between 20 and 60 days in SD animals. Hypothalamic SP levels increased in a similar manner in SD animals, but in LD animals the increment was less pronounced, with increased levels from day 20 to 40, followed by a plateau. In the anterior pituitary gland, NKA concentrations in LD animals increased at 40 days of age, with only slight increases afterward, but overall the increment curve was considerably flatter than for hypothalamic NKA. In SD animals, the increase of anterior pituitary NKA was much steeper than in LD animals. However, the total content of NKA in the AP was similar in both SD and LD animals, because the AP weight was considerably higher in LD- than in SD-exposed hamsters. These results showed that photoperiod did not markedly affect the developmental changes in hypothalamic NKA. The developmental changes in anterior pituitary NKA concentrations were considerably smaller than in the hypothalamus in LD animals, but in SD animals they were much steeper. NKA concentrations in the anterior pituitary were markedly affected by the photoperiod. Concentrations of NKA in the anterior pituitary of the Siberian hamster at the age of 15 days of age were already higher than in the anterior pituitary of adult rats or Syrian hamsters.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1995

Isolation and culture of Sertoli cells from the testes of adult Siberian hamsters: analysis of proteins synthesized and secreted by Sertoli cells cultured from hamsters raised in a long or a short photoperiod.

In the present study, we describe two procedures for isolation and culture of Sertoli cells from the testes of adult Siberian hamsters. In procedure I, collagenase and pancreatin were used for differential enzymatic digestion of the tissue at 32 degrees C, and effects of several attachment factors were examined. Sertoli cells isolated from adult hamsters were not affected by addition of Na selenite, epidermal growth factor, insulin, and transferrin, with or without 5% fetal bovine serum, to Dulbecco's modified Eagle's medium + Ham's F-12. Significant increase in the yield and plating efficiency of Sertoli cells was achieved by developing a novel procedure (procedure II) for Sertoli cell isolation. In this procedure, testicular tissue was exposed to only one enzyme (collagenase I) for two consecutive digestions at 37 degrees C, and the total period of enzymatic exposure was reduced relative to that of procedure I. Another objective of this study was to compare the functions of Sertoli cells isolated from spermatogenetically active and inactive adult testes. Isolated Sertoli cells from 60 +/- 5-day-old hamsters raised in long day conditions (LD, 16L:8D) or in short day conditions (SD, 6L:18D) were stimulated with FSH and testosterone in the presence of 35S-methionine for 24 h on Day 4 of culture. The medium was concentrated, and equal amounts of radioactive proteins from LD and SD hamster Sertoli cell cultures were analyzed by two-dimensional PAGE. Compared to Sertoli cells derived from SD hamsters, Sertoli cells from LD animals produced greater amounts of two secretory proteins and a smaller amount of one.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Effects of bovine growth hormone (bGH) transgene expression or bGH treatment on reproductive functions in female mice.

Both physiological and excessive levels of growth hormone (GH) can affect reproductive functions. Overexpression of human (h) or bovine (b) GH in transgenic female mice was previously reported to be associated with reproductive deficits. The objectives of the present study were to determine the age of onset of puberty, the length of the estrous cycle, and the ovulation rate in transgenic and normal mice from a line expressing bGH with the phosphoenolpyruvate carboxykinase (PEPCK) promoter and characterized by very high levels of transgene expression. Transgenic females reached puberty, defined as the appearance of the vaginal introitus, earlier than their normal littermates, but at a higher body weight. Compared to normal animals, an increased number of transgenic females failed to mate during the 15-day period of observation, and pregnancy rates were reduced. However, ovulation rates, as estimated by counting CL and implantation sites on Day 7 postcoitum, were increased in transgenic females. Plasma bGH levels in transgenic females ranged from 700 to 2200 ng/ml and were negatively correlated with fertility. To assess the effect of bGH on the ovulation rate in non-transgenic mice, normal females were paired with normal males and injected for up to 3 days with either 0.75 mg bGH/day or 0.30 mg bGH/day (injected as a single dose or as 0.15 mg twice daily). Data from animals that mated after at least 2 days of bGH treatment were analyzed. The ovulation rate was increased in females treated with 0.75 mg bGH/day, as compared to controls, and in females injected with 0.15 mg bGH twice daily as compared to those given 0.3 mg bGH/day and to controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Infertility in transgenic mice overexpressing the bovine growth hormone gene: luteal failure secondary to prolactin deficiency.

Overexpression of growth hormone (GH) in transgenic mice is associated with various degrees of impairment of female reproductive functions. Transgenic PEPCK.bGH mice express high GH levels, and only around 20% of the females will carry gestation to Day 7. The objective of the present study was to investigate luteal function in PEPCK.bGH mice during early pregnancy, when CL are fully dependent on the pituitary. Plasma progesterone levels measured on Days 2 or 7 postcoitum (p.c.) were lower in transgenic than in normal females. In transgenic females with a previous history of infertility, daily injections of 1 mg progesterone starting on Day 2 p.c. significantly increased the proportion of animals pregnant on Day 7. When ovaries from transgenic mice were transplanted into ovariectomized normal littermates, the recipients exhibited normal vaginal cycles and responded to mating by vaginal cytology changes consistent with pseudopregnancy. In contrast, ovariectomized transgenic females bearing transplants of ovaries from normal mice had slightly prolonged estrous cycles and failed to become pseudopregnant after mating. Plasma progesterone levels on Days 2 and 7 p.c. in normal females with transgenic ovaries were not different from plasma progesterone levels measured in normal females into which normal ovaries had been transplanted. Twice-daily injections of 100 micrograms of prolactin (PRL) in saline or in polyvinylpyrrolidone starting on the evening of Day 2 p.c. were able to rescue luteal function. The proportion of PRL-injected transgenic animals that were pregnant on Day 7 was significantly higher than that of saline-injected transgenic controls and resembled the pregnancy rate of normal animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Infertility in transgenic mice overexpressing the bovine growth hormone gene: disruption of the neuroendocrine control of prolactin secretion during pregnancy.

Transgenic female mice overexpressing the bovine growth hormone (bGH) gene with the phosphoenolpyruvate carboxykinase (PEPCK) promoter exhibit severe reproductive deficits. Although these animals ovulate and conceive normally, pregnancy is arrested due to luteal failure, leading to the loss of embryos during early gestation. The results of replacement therapy suggested that luteal failure was secondary to prolactin (PRL) deficiency. The objective of this study was to examine the neuroendocrine control of PRL secretion during early pregnancy in PEPCKbGH-1 transgenic mice. Normal and transgenic littermates were killed by decapitation on Day 7 postcoitum (p.c.) at 1500, 1800, or 2100 h, i.e., the period including the expected diurnal PRL surge in pregnant mice. In normal females, plasma PRL levels were significantly elevated at 1800 h when compared to the levels measured at 1500 or 2100 h, but no temporal variation in PRL levels was found in transgenic mice. In normal females, the content of dopamine in the median eminence was reduced at 1800 h, i.e., at the time of the PRL surge. In contrast, no temporal changes were detected in the median eminence dopamine content in transgenic mice. Twice-daily injections of domperidone, a dopamine receptor blocker, increased the incidence of pregnancy in transgenic females. After treatment with aromatic amino acid decarboxylase inhibitor NSD-1015 on Day 7 p.c., plasma levels of PRL were similarly elevated in transgenic and normal females. However, the accumulation of 5-hydroxytryptophan (5-HTP) in the medial basal hypothalamus after this treatment was significantly smaller in transgenic than in normal females.(ABSTRACT TRUNCATED AT 250 WORDS)

5-Hydroxytryptophan↗
PubMed1995

Growth hormone-binding protein in normal mice and in transgenic mice expressing bovine growth hormone gene.

The levels and characteristics of growth hormone (GH)-binding protein (GHBP) and the distribution of GH in peripheral circulation between the free and the bound fractions were studied in three lines of transgenic mice with various degrees of overexpression of bovine (b) GH gene. Two serum fractions bound GH specifically: one with low affinity and high capacity (GHBPI) and one with high affinity and low capacity (GHBPII). The GHBP binding capacity in normal mice (both sexes), transgenic male mice that express the metallothionein-I-hybrid bGH genes, transgenic female mice that express phosphoenolpyruvate carboxykinase (PEPCK)-bGH hybrid genes (PEPCK-bGH-1), and transgenic PEPCK-bGH-5 animals was 1.1 +/- 0.2, 2.0 +/- 0.1, 3.0 +/- 0.1, and 3.9 +/- 0.6 pmol/ml serum, respectively. The amount of GH bound to GHBP in transgenic animals vs. normal siblings was increased 1.8-, 2.5-, and 3.9-fold in these three lines. Consequently, the levels of GH-GHBP complexes in the circulation of PEPCK-bGH-1 transgenic mice were increased approximately 10-fold. Specific GHBP radioimmunoassay confirmed a threefold increase in GHBP in PEPCK-bGH-1 transgenic animals. The levels of GHBP were not significantly correlated to serum GH within or between lines, perhaps due to elevation of serum GH in PEPCK-bGH mice above the level producing maximal response. From these and previous studies, we conclude that life-long exposure to supranormal GH levels leads to major shifts in GH binding in the circulation and in the GH target organs.

Animals↗
PubMed1995

Effects of tachykinins on the secretory activity of rat Sertoli cells in vitro.

In the present study we investigated the effects of various tachykinins on the secretory activity of rat Sertoli cells in vitro. Sertoli cells were isolated from testes of immature Sprague Dawley rats, cultured for 4 days and thereafter incubated with three concentrations (0.1 pM, 1 pM or 100 pM) of substance P (SP), neurokinin A (NKA), neuropeptide K (NPK) or neuropeptide gamma (NPG) for 24 h. Levels of transferrin and lactic acid were determined in the culture media and expressed per micrograms of cellular DNA. Among all the peptides studied, NPG exhibited the greatest stimulatory effect on the release of transferrin and lactate, with NKA and NPK being less potent and SP being the least potent. Also, the effects of tachykinins on the aromatase activity of cultured Sertoli cells, as reflected by their ability to metabolize testosterone to estradiol (E2), were studied. No stimulatory effect was observed at lower concentrations (1 pM), while at 100 pM both NPG and NKA increased estradiol levels in the medium. SP and NPK had no significant effect on estradiol levels in the medium. This study reveals that tachykinins are able to influence the secretory activity of Sertoli cells, and that some of these peptides can also enhance the aromatase activity. Thus there is a possibility that tachykinins may have a physiological role as modulators of the function of Sertoli cells.

Animals↗
PubMed1995

Number and size of islets of Langerhans in pregnant, human growth hormone-expressing transgenic, and pituitary dwarf mice: effect of lactogenic hormones.

To determine the effects of lactogenic hormones on pancreatic islet size and numbers, islets of 3-month-old female mice were intravitally stained by an ip injection of an alkaline-alcohol solution of diphenylthiocarbazone (dithizone; 100 micrograms/g BW). After 15 min, animals were killed, and pancreases were removed, diced, cleared in glycerol, and whole mounted on slides. Major and minor axes of Zn dithizoate-stained islets were measured at x40 magnification. Islet areas and volumes were calculated. Animals and appropriate controls studied included 16-day pregnant, two lines of human GH-expressing transgenic, and two lines of pituitary PRL- and GH-deficient dwarf mice. Islet numbers per pancreas ranged from about 500-1200 in all groups except the transgenic mice, in which two of five animals in one group and one of five in the other showed significant increases in islet numbers (> 3 x SD control mean). In all cases, significant (P < 0.05) changes in both islet area and volume occurred. Area increased 2-fold in both pregnant and transgenic mice and decreased by a similar amount in dwarf mice. Islet volume increased 2- and 3-fold in pregnant and transgenic animals, respectively, and decreased 2- to 5-fold in dwarf mice. Analysis of the distributions of islet sizes revealed that almost all of the volume increases in the pregnant and transgenic mice and the decreases in dwarf mice were accounted for by alterations in the numbers and sizes of large (diameter, > 150 microns) islets. Our results with dwarf mice show that maintenance of islet numbers is not dependent upon pituitary PRL or GH; however, results with transgenic mice suggest that prolonged high levels of lactogens may induce islet neogenesis. The islet area and volume results for all of the mice studied support the hypothesis that lactogenic hormones are potent regulators of islet mass.

Animals↗
PubMed1995

Photoperiod effects on neurohypophyseal and tuberoinfundibular dopamine metabolism in the male hamster.

Exposure of golden hamsters to a short photoperiod (< 12.5 h light/day) leads to suppression of gonadal function secondary to reduced gonadotropin and PRL secretion. PRL secretion is decreased despite a reduction of tuberoinfundibular dopaminergic activity. In the present study, the ability of photoperiod to affect tuberohypophyseal dopamine (DA) turnover was evaluated in long day (LD; 16 h of light, 8 h of darkness) and short day (SD; 8 h of light, 16 h of darkness) male hamsters. Exposure to SD led to decreases in testicular weight within 10 weeks and decreases in plasma PRL levels within 1 week. DA turnover in the neurointermediate lobe of the pituitary, as estimated by measuring the depletion of DA 60 min after tyrosine hydroxylase inhibition with alpha-methyl-p-tyrosine (250 mg/kg), was significantly elevated 1 and 4 weeks after transfer to SD, but returned by 10 weeks to the levels seen in LD animals. After 14 days of SD exposure an enhanced lactotroph sensitivity to DA was demonstrated and may also have contributed to suppression of PRL levels. Similarly to the findings of previous studies, DA turnover in the median eminence was depressed in animals housed in SD. The DA content of the anterior pituitary was not significantly affected by photoperiod. The data from this study suggest that decreases in PRL secretion associated with the transfer of hamsters from LD to SD conditions are at least in part caused by an increase in DA turnover by neurohypophyseal neurons. However, the involvement of other PRL-inhibiting or -stimulating factors in mediating the effects of photoperiod on PRL secretion cannot be ruled out.

Animals↗
PubMed1995

Developmental expression of the prolactin receptor gene in rat gonads.

The prolactin receptor (PRLR) is a member of the cytokine/prolactin/GH receptor family, and it is widely expressed in various mammalian tissues. Expression of the two different forms of PRLR, differing in the length of their cytoplasmic domains, was studied in rat gonads during fetal and postnatal development. The two forms of PRLR mRNA were analyzed by reverse transcription (RT)-PCR using primer pairs specific for the different forms. The specificity of the cDNA species generated by RT-PCR was verified by Southern hybridization using nested 32P-labeled oligonucleotides. The results indicated that both forms of PRLR mRNA are expressed in the rat testis and ovary, which is in agreement with previous reports. The onset of expression of the two PRLR forms occurs on day 14.5 of fetal life in rat testis. In the ovary, the long form of PRLR mRNA appears 1 day before the short form, i.e. these forms begin to be expressed on fetal days 14.5 and 15.5 respectively. In situ hybridization with antisense cRNA probes specific to each form of the PRLR mRNAs demonstrated specific hybridization of both forms, localized in Leydig cells from day 18.5 of fetal life and at the postnatal ages studied. Compared with our previous findings concerning the ontogeny of LH receptor gene expression, PRLR gene expression starts earlier in development and exhibits no sexual dimorphism. The presence of two forms of PRLR mRNA in the fetal gonads suggest that they might play differential roles in gonadal development and function.

Animals↗
PubMed1995

Assessment of the primary adrenal cortical and pancreatic hormone basal levels in relation to plasma glucose and age in the unstressed Ames dwarf mouse.

Peripheral glucose concentrations in mammals are maintained within very narrow limits to provide a continuous, uninterrupted supply of this nutrient to tissues. Numerous factors have been shown to influence and/or regulate glucose levels. One such influence is growth hormone (GH) produced by the pituitary somatotrophs. Several animal models of hyposomatotropism are available in which GH secretion or actions are suppressed due to genetic abnormalities. One such model, the Ames dwarf mouse (df/df), has arisen from an autosomal recessive mutation in which GH-, prolactin- (PRL), and thyroid-stimulating hormone (TSH)-producing cell types of the anterior pituitary fail to develop. The current investigation examined the effects of GH deficiency on glucose, insulin, and corticosterone levels using male and female df/df mice and their normal (Df/-) littermates. Additionally, old and young females of both genotypes were used to determine whether aging and GH deficiency interact to influence insulin, corticosterone or glucose levels in these animals. Plasma samples collected from unstressed animals (normal, df/df; young [5 months], old [17-19 months]; male, female) were used. Glucose levels were lower (P < 0.05) in df/df than in Df/- mice regardless of sex and age. A sex difference in Df/- animals was evident--young and old females had significantly lower levels of glucose when compared with young Df/- males. Plasma insulin was elevated (P < 0.05) in old df/df females compared with young df/df and Df/- females. Young Df/- males had the highest insulin levels compared with all genotype and age groups. This observation paralleled results from glucose measurements. Corticosterone levels were highest in young Df/- females and lowest in young Df/- males, with df/df animals falling between these values. Plasma corticosterone levels in old Df/- females did not differ from the values measured in dwarfs. The present findings indicate that glucose and factors affecting glucose levels are altered in the df/df mouse. These results provide new insights into the roles GH may play in glucose metabolism and perhaps also in adiposity which is a common characteristic of Df/- aged females from this line of mice.

Aging↗
PubMed1994

Sertoli cells in testes containing or lacking germ cells: a comparative study of paracrine effects using the W (c-kit) gene mutant mouse model.

BACKGROUND: Paracrine effects of germ cells on Sertoli cell structure were examined in a mouse model with the W locus (dominant white spotting) mutation in which animals with the W/Wv genotype (referred to as mutants) lack virtually all germ cells. RESULTS: Morphometric determination of Sertoli cell parameters in mutant and control (+/+) animals showed that although the testes of mutant animals were about eight times smaller than controls, the numbers of Sertoli cells in the two groups did not differ. Sertoli cell volume, Sertoli cell cytoplasmic and nuclear volumes, and Sertoli cell surface area in mutant animals were significantly smaller than in control animals. Organelle volumes and surface areas, expressed per cell, did not differ significantly in the two groups with one exception: the volume and surface area of smooth endoplasmic reticulum was significantly reduced in mutant animals. Plasma testosterone levels and tissue testosterone levels/testis were normal, indicating that the effects observed in the mutant animal were not a consequence of androgen insufficiency. Plasma FSH was elevated, probably as a consequence of germ cell depletion, and was thought not to affect Sertoli cell parameters observed. CONCLUSIONS: The data suggest that paracrine interactions with germ cells do affect Sertoli cells by modifying the amount of smooth endoplasmic reticulum. These data focus attention on the function of this abundant Sertoli cell organelle in promoting spermatogenesis.

Animals↗
PubMed1994

Vitamin D modulates the effects of follicle-stimulating hormone on Sertoli cell function and testicular growth in Siberian hamsters.

Sertoli cells from immature (18-20 day old) Siberian hamsters (Phodopus sungorus) raised in a long photoperiod (LD; 16hL:8hD) or a short photoperiod (SD; 6hL:18hD) were cultured and exposed to follicle-stimulating hormone (FSH) and/or vitamin D3 (D3) in vitro. D3 did not stimulate lactate production when added alone, but significantly augmented the stimulatory action of FSH on lactate production by Sertoli cells from both LD- and SD-exposed hamsters. Hamsters raised in LD or SD were injected daily with D3 for 10 days starting at 18 days of age. This treatment resulted in a significant increase in the testicular weight of hamsters raised in LD in which circulating FSH levels are high. In contrast, testicular weight was not altered by D3 treatment in SD hamsters in which circulating levels of FSH are low. We conclude that D3, probably after hydroxylation to 1,25(OH)2 vitamin D3, modulates the action of FSH on testicular growth and Sertoli cell function.

Animals↗
PubMed1994

Acute effects of rat growth hormone (GH), human GH and prolactin on proliferating rat liver cells in vitro: a study of mitotic behaviour and ultrastructural alterations.

Examination of livers from transgenic mice over expressing human growth hormone (hGH) revealed numerous alterations including a striking incidence of mitotic figures. The reason for increased proliferation is unclear, but could be related to effects of hGH, which is also acting as a lactogen in rodents. In order to identify some of the actions of GH, we have examined the effects of rat and human GH and rat prolactin on proliferation, as well as on morphological differentiation of normal rat liver cells in vitro. These cells, isolated from a 20-day-old rat, proliferate in culture, incorporate BrdU and are thus strikingly different from primary cultures of isolated hepatocytes, which typically are non-proliferating cells. Monolayers of these cells were treated with rat prolactin (rPRL), rat growth hormone (rGH), rPRL and rGH in combination, or hGH, for 24 hr. Subsequently, mitotic figures were counted and the cultures were processed for transmission electron microscopy. The incidence of mitotic figures was significantly increased by rPRL (27.4%) versus control (19%), while rGH (13%) and hGH (9.6%) significantly decreased proliferation. In controls, 2% of the proliferating cells were in prophase, approximately 12% in metaphase and approximately 15% in telophase. In contrast, rPRL caused a significant increase in the number of cells in prophase (14%) and reduced the number of cells in the other mitotic stages. hGH and rGH reduced the overall number of mitotic figures. Unexpectedly, the effects of rGH plus rPRL were different from the effect of hGH. In addition, each treatment caused distinct morphological changes of liver cell organelles.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Effects of delta 9-tetrahydrocannabinol on copulatory behavior and neuroendocrine responses of male rats to female conspecifics.

Male rats exposed to sexually receptive females, exhibit a rapid increase in plasma levels of luteinizing hormone (LH) and prolactin, and concomitant increases in noradrenergic activity in the medial basal hypothalamus (MBH) and median eminence (ME) as well as in dopaminergic activity in the MBH. Delta-9-tetrahydrocannabinol (THC; 5 mg/kg b.wt., PO), the chief psychoactive constituent of marijuana, blocked the MBH and ME noradrenergic response and the dopaminergic response in the MBH in male rats exposed for 20 min to sexually receptive females, and suppressed the expected increases in plasma LH and prolactin levels. Moreover, THC treatment decreased the percentage of animals exhibiting copulatory behavior and increased the latency periods to mount and intromit. These findings indicate that THC interferes with the neuroendocrine and behavioral responses of male rats to the presence of a receptive female.

Animals↗