PubMed Health⌕ Search

Biomedical subjects

K E Borg

Publications and source records attributed to K E Borg.

16 recordsLinked to original sources

Endocrine physiology in a patient-centered learning curriculum.

The medical curriculum at the University of North Dakota School of Medicine and Health Sciences has recently been redesigned into a problem-based/traditional hybrid model that utilizes an integrated organ systems-based approach to teach basic and clinical sciences. The number of lecture hours in general has been greatly reduced, and, in particular, lecture hours in physiology have been reduced by 65%. Students learn basic science in small groups led by a faculty facilitator, and students are responsible for a great deal of their own teaching and learning. The curriculum is centered around patient cases and is called patient-centered learning (PCL). The curriculum includes traditional lectures and laboratories supporting faculty-generated learning objectives. Endocrine physiology is taught in year one, utilizing four weeks of patient cases that emphasize normal structure and function of endocrine systems. Endocrine physiology is revisited in year two, which is primarily focused on pathobiology. The PCL curriculum, with emphasis on the endocrine component, is described in detail along with key portions of an endocrine case.

Education, Medical↗

The health-line--a method for collecting data on self-rated health over time: a pilot study.

BACKGROUND: There is a need for an instrument to record a life-course perspective of self-rated health. AIM: To test the "health-line", a simple, comprehensive method of collecting data on self-rated health over time. METHOD: In 1996, a questionnaire was mailed to people who in 1985 were aged between 25 and 34 years old and had a sick-leave spell >28 days with "back diagnoses". They were asked to rate their global health graphically with a "health-line" for the years 1985-95. Official data on sick leave and disability pension were obtained for the same period. In all, 37 out of 52 men and 60 out of 83 women answered; that is, they drew a health-line. RESULT: A statistically significant negative correlation between the mean number of absence days due to ill health and the health-line data was found for every year (r= -0.35 to -0.53; p<0.001) and for the whole period 1985-95 (r=-0.546; p<0.001) respectively. CONCLUSION: The method worked well and is well worth further development and testing.

Adult↗

Prolactin regulation of pim-1 expression: positive and negative promoter elements.

The lactogen-dependent rat Nb2 lymphoma is a useful model to investigate PRL signaling pathways that lead to regulation of gene transcription. A primary mechanism coupled to PRL receptor (PRLR) activation in Nb2 cells involves phosphorylation by Jak-family tyrosine kinases of one or more signal transducers and activators of transcription (Stat) factors which subsequently bind to gamma-interferon activation sequences (GAS) within promoter regions of target genes. However, it is presently unclear whether this mechanism is operative as a means for regulating PRL-induced gene expression to the exclusion of other signaling pathways. Previously, we reported that PRL directly stimulated rapid expression of the protooncogene, pim-1, at the mRNA and protein levels in lactogen-dependent Nb2-11 cells. In the present study, experiments were conducted to evaluate signaling mechanisms by which PRL regulates transcription of pim-1. Toward this end, a 1,268-bp segment upstream of the transcription initiation site of the 5'-pim-1 promoter and a series of deletion mutants were ligated upstream of the chloramphenicol acetylase transferase (CAT) gene in an expression vector that was introduced into FDC/Nb2 cells, a premyeloid line that stably expresses the intermediate form of the PRLR. Analysis of PRL-treated cultures indicated that two elements [distal (DE), -427 to -336 bp and proximal (PE), - 104 to -1] but not several GAS or GAS-like sequences were required for hormone activation of the pim-1 promoter. Moreover, treatment of Nb2-11 cells with PRL activated protein binding to these elements assessed by gel mobility shift assay. Deoxyribonuclease I (DNase I) protection experiments revealed a motif containing a nuclear factor-1 (NF-1, -224 to -217 bp) half-site that was hydrolyzed when exposed to extracts from PRL-treated cells but protected by proteins from unstimulated cells. Gel mobility shift analysis of this sequence showed decreased protein binding after PRL stimulation. It is concluded that the PRLR initiates pim-1 transcription by a mechanism that involves transcriptional activation by factors that stimulate the DE- and PE-sites and derepress a NF-1-containing element. Moreover, this mechanism appears to be independent of an interaction between Stat transcription factors and GAS-like elements present within the promoter.

Animals↗

Effects of photoperiod on testicular inhibin-alpha and androgen binding protein mRNA expression during postnatal development in Siberian hamsters, Phodopus sungorus.

The effects of short photoperiod (SPP) on testicular inhibin-alpha and androgen binding protein (ABP) mRNA expression were investigated in Siberian hamsters during postnatal development. Hamsters were raised in either long photoperiod (LPP; 16L:8D) or in a SPP (6L:18D). Hamsters were sacrificed at the following developmental ages: preweaning (18-20 days), immature (28-30 days), pubertal (38-40 days), postpubertal (48-50 days) and adult (60-62 days; n = 7-12 animals per group). Body and testicular weights were determined and plasma FSH levels were measured by validated RIA. As expected, testicular weight and circulating FSH levels were significantly lower in hamsters raised in SPP than in LPP animals. Photoperiod had no significant effect on body weight except during postpubertal age. The northern analyses of inhibin-alpha and ABP expression in the testes revealed that the corresponding relative mRNA levels were higher in animals exposed to SPP than in animals from LPP. These findings suggest that the testes of hamsters exposed to a SPP can synthesize inhibin-alpha and ABP, and we speculate that the release of these proteins may be regulated by photoperiod and the role of FSH in the control of inhibin-alpha and ABP gene expression in male Siberian hamsters may be minimal.

Androgen-Binding Protein↗

Functioning of the porcine pituitary-adrenocortical axis during neonatal development.

A study was conducted with neonatal boars to measure age-related changes in functioning of the pituitary-adrenocortical axis. Pigs were randomly assigned to control (n = 7-10/age) or treated (1-min restraint, n = 9-11/age) groups to be sampled at either 12, 19, or 26 days of age. Blood samples were taken via catheter 10 min before and 3, 10, and 20 min after restraint or at similar time intervals in controls. One day later, pigs were killed and adrenal glands obtained for ACTH receptor measurements. Basal plasma ACTH concentrations were greatest (p = 0.035) on day 12 when compared with later ages, but basal plasma cortisol concentrations were comparable at the three ages. Compared with controls, restraint elevated incremental plasma ACTH and cortisol responses at each age (p < 0.004). On day 12, maximal plasma ACTH (p = 0.0006) and incremental cortisol (p < 0.006) responses to restraint were greater than at later ages. Binding to adrenal ACTH receptors was greatest (p < 0.05) at day 13, which may help explain the apparently increased in vivo response of the adrenal gland to ACTH at this time. Restrained pigs had increased growth rates with increasing age (p = 0.016) whereas growth rates for control pigs did not differ with age. At day 27, 24 h after the 1-min restraint, body weights of restrained pigs exceeded those of control pigs (p = 0.045). At day 20, adrenal DNA and protein in pigs restrained 24 h previously were greater than in control pigs (p < 0.05). These data suggest age-related changes in functioning of the pituitary-adrenal axis in neonatal boars, and an absence of period during neonatal life when the porcine pituitary adrenocortical axis cannot respond to a stressor. The data also indicate both rapid and long-term responses of the adrenal to a very modest stressor and suggest an extreme sensitivity of neonatal pigs to environmental perturbations.

Adrenal Cortex↗

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↗

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↗

Semen characteristics, testicular size, and reproductive hormone concentrations in mature duroc, meishan, fengjing, and minzhu boars.

Chinese breeds of swine are known for their reproductive prolificacy and are noted for large litter size. The current investigation evaluated reproductive components of three breeds of Chinese boars in comparison to a contemporary site breed common in the U.S. Semen from postpubertal Duroc, Meishan, Fengjing, and Minzhu boars was collected during four seasons of the year. After each semen collection and evaluation period, boars were weighted and placed in a restraining chute for testicular measurements and blood sampling for measurement of FSH, testosterone, and inhibin. Although Duroc boars were 2 mo younger than Chinese boars, initial and final body weight and paired testis volume in Durocs were greater (p < 0.05) than in Chinese boars. Total spermatozoa per ejaculate was similar for Duroc and Minzhu boars, but was lower (p < 0.05) in Fengjing and Meishan boars. Progressive motility and sperm morphological characteristics were not affected by breed of boar. Serum FSH concentrations were markedly higher (p < 0.01) in Meishan and Fengjing boars than in other breeds, and concentrations were nearly 8-fold higher in Meishan than in Duroc boars. Breed differences in serum inhibin were essentially the inverse of those observed for FSH, with Durocs exhibiting the highest inhibin concentrations and Meishans exhibiting the lowest. Testosterone values were not different between breeds. However, testosterone concentrations fluctuated with season, and serum testosterone was highest during the fall of the year in all breeds. These results indicated that some reproductive characteristics differ dramatically between Duroc and Chinese breeds of boars. Breed differences existed in body size, testis size, sperm per ejaculate, ejaculate volume, and serum FSH and inhibin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Recombinant human follicle-stimulating hormone is capable of exerting a biological effect in the adult hypophysectomized rat by reducing the numbers of degenerating germ cells.

There is considerable controversy as to whether FSH can, under normal circumstances, exert an effect to promote spermatogenesis in the adult rat. Recombinant human FSH (rhFSH) was used to answer a more limited question relating to whether FSH is capable of exerting a biological effect in promoting adult spermatogenesis. Can a pure preparation of FSH prevent the regressive changes seen after hypophysectomy (Hx) in a short term experiment? To answer this question, five groups of adult rats were used as follows: pituitary-intact animals, 3-day hypophysectomized (Hx), 3-day Hx given 3 mg testosterone propionate (T)/day for 7 days, 3-day Hx given 22 IU rhFSH for 7 days, and 3-day Hx given saline vehicle for 7 days. Testis weight, seminiferous tubule diameter, analysis of four degenerating germ cell types, the relative amount of lipid, and the levels of FSH receptors showed that FSH could, in a significant manner, prevent the regressive changes accompanying Hx. FSH was not as effective as T in doing so, because the FSH values were always intermediate between T-maintained animals and those after long term Hx. The Leydig cell was eliminated as a possible source of FSH-stimulated T promotion of spermatogenesis, given that morphometry and tissue T assays indicated that no additional production of T was elicited by rhFSH. The assay system used to enumerate degenerating germ cells proved a very sensitive indicator of the ability of hormones to maintain cell viability in short term experiments. The data not only show that FSH can exert a biological effect, but that this effect is qualitatively similar to that seen after the administration of T in terms of the maintenance of viability of specific germ cell types. A hypothesis is presented whereby FSH and T, although the former acting by a second messenger system and the latter by binding to nuclear receptors, can stimulate the genome to exert similar qualitative effects promoting the viability of germ cells.

Animals↗

Association between low birth weight and increased adrenocortical function in neonatal pigs.

This study examined differences in adrenocortical function between low- and high-birth-weight female neonatal pigs. Pigs born to unilaterally hysterectomized, ovariectomized sows were grouped by birth weight; "small" were < or = 1.2 kg and "large" were > 1.2 kg. Pigs were cross-fostered such that each sow had six to eight pigs that were either small or large. At 3 or 7 d of age a blood sample was obtained by venipuncture, pigs were killed, and adrenocortical cells were isolated. Adrenal weights (milligrams/kilogram BW) in small pigs were 46% greater (P = .001) than those in large pigs at both ages. Compared with those in large pigs, plasma cortisol concentrations were 70% greater (P = .006) in small pigs at 3 d and 199% greater at 7 d of age. Sensitivity of adrenocortical cell response to ACTH was enhanced at both ages in small pigs (P = .001). Corticosteroid binding globulin (CBG) binding capacity in small pigs was 75% greater (P = .03) than that in large pigs at 3 d and 26% greater at 7 d of age. Significant negative correlations existed between birth weight and relative adrenal weight, plasma cortisol, slopes of in vitro adrenocortical cell response curves to ACTH, and CBG binding capacity, irrespective of birth weight group classification. Such data indicate an association between adrenal function during early neonatal life and birth weight in female pigs. The current study does not indicate whether increased adrenal function causes or merely reflects conditions associated with low birth weight. However, we hypothesize that increased adrenal function is initiated prenatally and causes some instances of low birth weight.

Adrenal Cortex↗

Prolactin and growth hormone clearance in neonatal boars.

The pharmacokinetics of prolactin (PRL) and growth hormone (GH) are not known in neonatal pigs. In this study, six boars, ages 13 and 26 d, were used to determine metabolic clearance rate (MCR), half-life (t1/2), and volume of distribution (Vd) of immunoreactive porcine PRL (ipPRL) and immunoreactive porcine GH (ipGH). Blood samples were collected through indwelling jugular catheters at 0, 1, 2.5, 5, 10, 15, 30, 45, and 60 min after a 20 ng/g of BW (per hormone) cocktail of porcine PRL and GH. Analysis of the ipPRL disappearance curves indicated an apparent MCR of 13.79 +/- 2.45 and 23.79 +/- 4.10 mL/min for boars at 13 and 26 d of age, respectively (P = .0008). The t1/2 of ipPRL did not differ between ages (P = .9201). The apparent MCR of ipGH at 13 and 26 d were 10.60 +/- 2.09 and 27.30 +/- 4.55 mL/min, respectively, and this difference was still evident after adjustment for BW (P = .0465). The ipGH t1/2 decreased with age (P = .0232), 21.32 +/- 2.55 vs 13.57 +/- 3.35 min for 13 and 26 d, respectively. The apparent distribution volume for ipPRL was higher than that for ipGH at both ages (P = .0021). Within each age, the apparent MCR of ipGH and ipPRL did not differ significantly. These data represent the first clearance measures reported for ipPRL and ipGH in neonatal pigs and indicate that under the conditions of this study the apparent MCR of ipPRL and ipGH are similar but change significantly during early development.

Animals↗

Effects of sexual experience, season, and mating stimuli on endocrine concentrations in the adult ram.

Two behavioral trials were conducted to determine the endocrine response of cortisol (C), luteinizing hormone (LH), testosterone (T), prolactin (PRL), and growth hormone (GH) in adult rams during exposure to estrous ewes during the breeding and nonbreeding seasons. One-half of the rams in each season were sexually experienced (SE) and the remainder were sexually inexperienced (SI). All SE rams (100%) achieved at least one ejaculation, but only 33% (summer) and 67% (fall) SI rams achieved ejaculation. In the fall, mean C, T, and GH concentrations were elevated (P less than .001) compared to values measured in the summer, whereas LH and PRL levels were higher (P less than .01) in the summer. Overall levels of C, LH, T, and PRL were higher (P less than .05) in SE rams than in SI rams. Mean GH concentration was higher (P less than .10) in SI than in SE rams during restricted and complete access to estrous ewes. In general, LH, PRL, and GH responses were similar during restricted and complete access to females for both SE and SI rams. Cortisol levels were higher (P less than .06) during periods of mating and T levels were higher (P less than .001) during periods where activity was limited to courtship behavior (nasogenital investigation). Correlations of hormones to reproductive behaviors indicated that mounting and intromission were associated with elevations in C and PRL, whereas elevated LH and T tended to be associated with courtship behaviors. Correlations between GH and behaviors were inconsistent. However, there was an increased coincidence between time of female exposure and hormonal response that occurred in the fall; brief exposure to estrous ewes resulted in increases in concentrations of all hormones examined. The most consistent response was observed in sexually experienced rams during restricted access to females during the breeding season. These results provide new information on the effects of season and level of sexual experience upon hormonal and behavioral characteristics of the ram during mating activity.

Animals↗

Effects of pretreatment with adrenocorticotropin on endocrine and behavioral responses of bulls to sexual activity.

Peripheral concentrations of cortisol, growth hormone and testosterone were determined in two experiments which examined the endocrine and behavioral responses of sexually mature Angus bulls to an estrous female (Experiment 1) and to female exposure 5 hours following an adrenocorticotropin (ACTH) injection (Experiment 2). Sexual activity of bulls in Experiment 1 significantly increased levels of cortisol when compared with concentrations before exposure to a female. Administration of ACTH in Experiment 2 consistently elevated levels of cortisol by 30-fold (P<0.01) when compared with pre-ACTH concentrations. This heightened level of cortisol persisted throughout the period of exposure to an estrous cow, although a gradual decline in cortisol concentrations occurred over time (P<0.05). In Experiment 1, growth hormone profiles tended to increase in response to sexual activity (P<0.10), whereas in Experiment 2, growth hormone increased in response to ACTH administration (P<0.01) and to female exposure (P<0.01). Concentrations of testosterone were unaffected (P>0.10) by mating activity in Experiment 1. In Experiment 2, acute suppression (P<0.01) in testosterone concentrations 5 hours after ACTH administration coincided with the exposure period to the estrous female. Frequencies of mounting behavious (penis extension, mounting, intromission and ejaculation) exhibited by ACTH-treated bulls were significantly lower compared with the frequencies two days earlier. Exogenous ACTH administration suppressed reproductive behaviors of bulls and altered secretion of cortisol, growth hormone and testosterone. Furthermore, these data provide evidence that specific mating behaviors of the bull can be influenced by circulating steroids.

Journal Article↗

Cortisol, growth hormone, and testosterone concentrations during mating behavior in the bull and boar.

Two experiments were conducted to evaluate peripheral concentrations of cortisol (C), growth hormone (GH), and testosterone (T) in bulls and boars during mating and to correlate mating behaviors with endocrine secretion in the presence of an estrous female. In Exp. 1, six sexually inexperienced mature bulls were bled every 15 min for 2 h before and 2 h after a 30-min exposure to a single, restrained, estrous cow; sampling occurred every 5 min during exposure. In Exp. 2, six sexually experienced boars were bled similarly before and after exposure to a sow and every 5 min during a 15-min exposure to a freely moving, estrous sow. Behavioral events recorded during exposure to a female included the following: flehmen responses (bulls only), mounts, penis extensions, intromissions, ejaculations, and time to first mount and first ejaculation. Of the six bulls, four completed at least one service (intromission + ejaculation), and three of six mounted the estrous cow eight or more times. Completion of one or more services resulted in significant elevations in serum C and GH concentrations, but not T concentrations, during the exposure period. Bulls mounting eight or more times also experienced significant elevations in C concentrations during exposure. Three of six boars completed at least one service. Servicing and mounting the sow fewer than five times were both associated with significant elevations in serum C concentrations. Serum concentrations of T were also elevated as a result of exposure to an estrous sow. Collectively, these data support the suggestion that specific events during natural mating activity can alter endocrine secretions of C and GH in bulls and C and T in boars.

Animals↗

Hormonal regulation of spermatogenesis in the hypophysectomized rat: FSH maintenance of cellular viability during pubertal spermatogenesis.

The potential for follicle-stimulating hormone (FSH) to promote germ-cell survival and the cellular sites of FSH action were studied using a gonadally maturing (pubertal), hypophysectomized (Hx) rat model in which residual testosterone (T) activity was blocked by injections of an androgen-receptor antagonist, flutamide. Recombinant human FSH was given to androgen-deprived and androgen-blocked male rats at 27 days of age to determine maintenance of individual germ-cell types at 35 days of age. Follicle-stimulating hormone significantly increased testis weights and tubular diameters as compared with Hx and Hx-flutamide controls, although testis weights in FSH-treated animals were significantly lower than in pituitary-intact animals. Morphometric assays to determine ratios of germ cells to Sertoli cells and to determine the number of germ cells present per hour of development showed that the population of type A spermatogonia in the early stages of the cycle was not responsive to FSH. Follicle-stimulating hormone had a marked ability to maintain cell viability in the rapid, successive divisions that begin in the latter part of the cycle and that continue through the next cycle (i.e., from type A1 to A4 and from intermediate spermatogonia to type B spermatogonia to preleptotene spermatocytes to leptotene/zygotene spermatocytes to young pachytene spermatocytes). The data also suggest T responsiveness of these cell types since the Hx-FSH-flutamide group showed lower cell viability at the aforementioned steps when compared with the Hx-FSH group. Too few cell types were present at subsequent phases of spermatogenesis to allow a sensitive determination of FSH activity in the maintenance of cell viability. The data show the potential of FSH in the absence or relative absence of T activity to maintain cell viability. These data support the concept of overlapping and synergistic (or additive) effects of T and FSH in the immature rat and identify the cellular sites of FSH action.

Androgen Antagonists↗