Distribution of cytochrome P-450 4A and 4F isoforms along the nephron in mice

2003 ◽  
Vol 284 (1) ◽  
pp. F95-F102 ◽  
Author(s):  
David E. Stec ◽  
Averia Flasch ◽  
Richard J. Roman ◽  
Jared A. White
Keyword(s):  
Sex Differences ◽  
Male Mice ◽  
Renal Vasculature ◽  
Male And Female ◽  
Female Mice ◽  
Nephron Segments ◽  
Renal Vessel ◽  
Proximal Tubular ◽  
Renal Tubular ◽  
Renal Vascular

The production of 20-hydroxyeicosatetraenoic acid (20-HETE) in the kidney is thought to be involved in the control of renal vascular tone and tubular sodium and chloride reabsorption. 20-HETE production in the kidney has been extensively studied in rats and humans and occurs primarily via the actions of P-450 enzymes of the CYP4A and -4F families. Recent advancements in molecular genetics of the mouse have made it possible to disrupt genes in a cell-type-specific fashion. These advances could help in the creation of models that could distinguish between the vascular and tubular actions of 20-HETE. However, isoforms of the CYP4A and -4F families that may be responsible for the production of 20-HETE in the vascular and tubular segments in the kidney of the mouse are presently unknown. The goal of this study was to identify the isoforms of the CYP4A and -4F families along the nephron by RT-PCR of RNA isolated from microdissected renal blood vessels and nephron segments from 16- to 24-wk-old male and female C57BL/6J mice. CYP4A and -4F isoforms were detected in every segment analyzed, with sex differences only observed in the proximal tubule and glomeruli. In the proximal tubular segments from male mice, the 4A10 and -12 isoforms were present, whereas the 4A10 and -14 isoforms were detected in segments from female mice. In glomeruli, sex differences in the expression pattern of CYP4F isoforms were also observed, with male mice expressing the 4F13, -14, and -15 isoforms, whereas female mice expressed the 4F13, -16, and -18 isoforms. These results demonstrate that isolated nephron and renal vessel segments express multiple isoforms of the CYP4A and -4F families; therefore, elimination of a single CYP4A or -4F isoform may not decrease 20-HETE production in all nephron segments or the renal vasculature of male and female mice. However, the importance of CYP4A vs. -4F isoforms to the production of 20-HETE in each of these renal tubular and vascular segments of the mouse remains to be determined.

Sex Differences in the Relation Between Frailty and Endothelial Dysfunction in Old Mice

2021 ◽  
Author(s):  
Jazmin A Cole ◽  
Mackenzie N Kehmeier ◽  
Bradley R Bedell ◽  
Sahana Krishna Kumaran ◽  
Grant D Henson ◽  
...  
Keyword(s):  
Sex Differences ◽  
Endothelial Function ◽  
Vascular Function ◽  
Mesenteric Artery ◽  
Frailty Index ◽  
Mesenteric Arteries ◽  
Male Mice ◽  
Male And Female ◽  
Female Mice ◽  
Age Related

Abstract Vascular endothelial function declines with age on average, but there is high variability in the magnitude of this decline within populations. Measurements of frailty, known as frailty index (FI), can be used as surrogates for biological age, but it is unknown if frailty relates to the age-related decline in vascular function. To examine this relation, we studied young (4-9 months) and old (23-32 months) C57BL6 mice of both sexes. We found that FI was greater in old compared with young mice, but did not differ between old male and female mice. Middle cerebral artery (MCA) and mesenteric artery endothelium-dependent dilation (EDD) also did not differ between old male and female mice; however, there were sex differences in the relations between FI and EDD. For the MCA, FI was inversely related to EDD among old female mice, but not old male mice. In contrast, for the mesenteric artery, FI was inversely related to EDD among old male mice, but not old female mice. A higher FI was related to a greater improvement in EDD with the superoxide scavenger TEMPOL in the MCAs for old female mice and in the mesenteric arteries for old male mice. FI related to mesenteric artery gene expression negatively for extracellular superoxide dismutase (Sod3) and positively for interleukin-1β (Il1b). In summary, we found that the relation between frailty and endothelial function is dependent on sex and the artery examined. Arterial oxidative stress and pro-inflammatory signaling are potential mediators of the relations of frailty and endothelial function.

scholarly journals Sex differences in renal and metabolic responses to a high-fructose diet in mice

2015 ◽  
Vol 308 (5) ◽  
pp. F400-F410 ◽  
Author(s):  
Nikhil Sharma ◽  
Lijun Li ◽  
C. M. Ecelbarger
Keyword(s):  
Sex Differences ◽  
Glucose Transporter ◽  
Collecting Duct ◽  
Urine Volume ◽  
Thick Ascending Limb ◽  
Male Mice ◽  
Male And Female ◽  
Female Mice ◽  
High Fructose Diet ◽  
High Fructose

High fructose intake has been associated with increased incidences of renal disease and hypertension, among other pathologies. Most fructose is cleared by the portal system and metabolized in the liver; however, systemic levels of fructose can rise with increased consumption. We tested whether there were sex differences in the renal responses to a high-fructose diet in mice. Two-month-old male and female C57BL6/129/SV mice ( n = 6 mice per sex per treatment) were randomized to receive control or high-fructose (65% by weight) diets as pelleted chow ad libitum for 3 mo. Fructose feeding did not significantly affect body weight but led to a 19% and 10% increase in kidney weight in male and female mice, respectively. In male mice, fructose increased the expression (∼50%) of renal cortical proteins involved in metabolism, including glucose transporter 5 (facilitative fructose transporter), ketohexokinase, and the insulin receptor (β-subunit). Female mice had lower basal levels of glucose transporter 5, which were unresponsive to fructose. However, female mice had increased urine volume and plasma K+ and decreased plasma Na+ with fructose, whereas male mice were less affected. Likewise, female mice showed a two- to threefold reduction in the expression Na+-K+-2Cl− cotransporter 2 in the thick ascending limb and aquaporin-2 in the collecting duct with fructose relative to female control mice, whereas male mice had no change. Overall, our results support greater proximal metabolism of fructose in male animals and greater distal tubule/collecting duct (electrolyte homeostasis) alterations in female animals. These sex differences may be important determinants of the specific nature of pathologies that develop in association with high fructose consumption.

scholarly journals Sex differences in adaptive downregulation of pre-macula densa sodium transporters with ANG II infusion in mice

2010 ◽  
Vol 298 (1) ◽  
pp. F187-F195 ◽  
Author(s):  
Swasti Tiwari ◽  
Lijun Li ◽  
Shahla Riazi ◽  
Veerendra K. Madala Halagappa ◽  
Carolyn M. Ecelbarger
Keyword(s):  
Sex Differences ◽  
Plasma Testosterone ◽  
Sodium Reabsorption ◽  
Thick Ascending Limb ◽  
Ang Ii ◽  
Male Mice ◽  
Male And Female ◽  
Female Mice ◽  
Sodium Transporters ◽  
Pressure Natriuresis

An increase in blood pressure (BP) due to angiotensin II (ANG II) infusion or other means is associated with adaptive pressure natriuresis due to reduced sodium reabsorption primarily in proximal tubule (PT) and thick ascending limb (TAL). We tested the hypothesis that male and female mice would show differential response to ANG II infusion with regard to the regulation of the protein abundance of sodium transporters in the PT and TAL and that these responses would be modulated by aging. Young (∼3 mo) and old (∼21 mo) male and female mice were infused with ANG II at 800 ng·kg body wt−1·min−1 by osmotic minipump for 7 days or received a sham operation. ANG II increased mean arterial pressure (MAP), measured by radiotelemetry, significantly more in male mice of both ages (increased ∼30–40 mmHg), compared with females (increased ∼15–25 mmHg). On day 1, MAP was also significantly increased in old mice, relative to young ( P = 0.01). ANG II infusion was associated with a significant decline in plasma testosterone (to <30% of control male) in male mice and rise in young female mice (to 478% of control female). No sex differences were found in the upregulation of the sodium hydrogen exchanger abundance on Western blots observed with ANG II infusion or the downregulation of the sodium phosphate cotransporter; however, aging did impact on some of these changes. Male mice (especially young) also had significantly reduced levels of the TAL bumetanide-sensitive Na-K-2Cl cotransporter (to 60% of male control), while young females showed an increase (to 126% of female control) with ANG II infusion. These sex differences do not support impaired pressure natriuresis in male mice, but might reflect a greater need and attempt to mount an appropriately BP-metered natriuretic response by additional downregulation of TAL sodium reabsorption.

Sex differences in the development of angiotensin II-induced hypertension in conscious mice

2005 ◽  
Vol 288 (5) ◽  
pp. H2177-H2184 ◽  
Author(s):  
Baojian Xue ◽  
Jaya Pamidimukkala ◽  
Meredith Hay
Keyword(s):  
Sex Differences ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Male Mice ◽  
Intact Male ◽  
Baroreflex Control ◽  
Angiotensin System ◽  
Male And Female ◽  
Female Mice ◽  
Induced Hypertension

Sex has an important influence on blood pressure (BP) regulation. There is increasing evidence that sex hormones interfere with the renin-angiotensin system. Thus the purpose of this study was to determine whether there are sex differences in the development of ANG II-induced hypertension in conscious male and female mice. We used telemetry implants to measure aortic BP and heart rate (HR) in conscious, freely moving animals. ANG II (800 ng·kg−1·min−1) was delivered via an osmotic pump implanted subcutaneously. Our results showed baseline BP in male and female mice to be similar. Chronic systemic infusion of ANG II induced a greater increase in BP in male (35.1 ± 5.7 mmHg) than in female mice (7.2 ± 2.0 mmHg). Gonadectomy attenuated ANG II-induced hypertension in male mice (15.2 ± 2.4 mmHg) and augmented it in female mice (23.1 ± 1.0 mmHg). Baseline HR was significantly higher in females relative to males (630.1 ± 7.9 vs. 544.8 ± 16.2 beats/min). In females, ANG II infusion significantly decreased HR. However, the increase in BP with ANG II did not result in the expected decrease in HR in either intact male or gonadectomized mice. Moreover, the slope of the baroreflex bradycardia to phenylephrine was blunted in males (−5.6 ± 0.3 to −2.9 ± 0.5) but not in females (−6.5 ± 0.5 to −5.6 ± 0.3) during infusion of ANG II, suggesting that, in male mice, infusion of ANG II results in a resetting of the baroreflex control of HR. Ganglionic blockade resulted in greater reduction in BP on day 7 after ANG II infusion in males compared with females (−61.0 ± 8.9 vs. −36.6 ± 6.6 mmHg), suggesting an increased contribution of sympathetic nerve activity in arterial BP maintenance in male mice. Together, these data indicate that there are sex differences in the development of chronic ANG II-induced hypertension in conscious mice and that females may be protected from the increases in BP induced by ANG II.

scholarly journals Iba1+ cell density and morphology classification at postnatal day 10 in four hippocampal subregions of female and male C57BL/6J mice

2021 ◽  
Author(s):  
Danielle Guez-Barber ◽  
Max Wragan ◽  
Dana Raphael ◽  
Haley M. Phillips ◽  
Kira Lu ◽  
...  
Keyword(s):  
Sex Differences ◽  
Cell Density ◽  
Female Rats ◽  
Male Rats ◽  
Lower Percentage ◽  
Male Mice ◽  
Male And Female ◽  
Female Mice ◽  
Mouse Hippocampus ◽  
The Brain

Microglia maintain normal brain function and support the brain′s response to disease and injury. The hippocampus is an area of focus for microglial study due to its central role in numerous behavioral and cognitive functions. Interestingly, microglia and related cells in the hippocampus and throughout the brain are distinct in male vs. female rodents, even in early life. Indeed, postnatal day (P)-dependent sex differences in number, density, and morphology of microglia-like cells have been reported in certain hippocampal subregions. For example, P3 female mice have more phagocytic microglia in dentate gyrus (DG) molecular layer (Mol) and CA1-3 stratum oriens (SO) regions vs. male mice, while P8 — but not P15 — male rats have more volume immunoreactive for markers of microglia-like cells (Iba1 and CD68) in the CA1 stratum radiatum (SR) vs. female rats. In the mouse, P10 is roughly equivalent to human term gestation, making it a common time point to study for many translationally-relevant neurobiological processes. However, sex differences in hippocampal microglia have not been examined in the P10 mouse hippocampus. In addition, key subregions of the hippocampus — CA3 SR, DG hilus — have not yet been assessed for sex differences in microglia. To address these knowledge gaps, we quantified Iba1+ cell densities and classified Iba1+ cell morphology in P10 male and female C57BL/6J mice. Four subregions in the bilateral anterior hippocampus were analyzed in 40-μm coronal sections: DG Mol (Mol), DG Hilus, CA1 SR and stratum lacunosum moleculare (CA1), and CA3 SR and stratum lucidum (CA3). Light microscope images (40x) were analyzed offline for Iba1+ cell density and morphology by an observer blind to sex. The morphology of each Iba1+ cell was used to place cells into one of four previously-published categories: Round or ameboid (round-ish soma, no processes), Stout (round-ish soma, short process), Thick (irregular soma with few, thick processes), or Thin (irregular soma with multiple thin processes). Analysis of Iba1+ cell density shows no difference between male and female mice in Mol, Hilus, CA3, or CA1 (male n=6, female n=7). However, morphology classification shows a sex-dependent difference in the Mol and Hilus, with female mice having a greater percentage of Thick Iba1+ cells vs. male mice (Mol, Hilus), and a lower percentage of Thin Iba1+ cells vs. male mice (Mol). With our analysis, it is unclear whether this greater percentage of thick and lower percentage of thin Iba1+ cells in the female vs. male hippocampus means Iba1+ microglia in female mice are ″younger″ or ″more active″ than those in male mice. However, these data are important as they reveal sex differences in Iba1+ microglia in the P10 mouse hippocampus. We discuss these results in the context of the large literature on sex differences in rodent microglia in the early postnatal period.

Mode of Inheritance of Emotionality in the Mouse (Mus Musculus): Sex Differences and the Effects of Trials and Illumination

1976 ◽  
Vol 39 (1) ◽  
pp. 247-256 ◽  
Author(s):  
Charles L. Goodrick
Keyword(s):  
Sex Differences ◽  
Inbred Mice ◽  
Male Mice ◽  
Illumination Condition ◽  
Male And Female ◽  
Female Mice ◽  
Group Sex ◽  
Hybrid Mice ◽  
Territorial Marking ◽  
Mode Of Inheritance

Inbred and hybrid mice ( N = 720) were tested in an open field to determine elimination differences as a function of inbred group, sex, trials, and illumination condition and to determine mode of inheritance of elimination. A/J, BALB/CJ, and DBA/2J inbred mice were more emotional than C57BL/6J inbred mice, male mice were more emotional than female mice, and emotionality increased as a function of trials. Emotionality was significantly lower for mice tested with dim illumination than for mice tested with bright illumination. Under the condition of bright illumination, the mode of inheritance of emotionality was dominant for both male and female mice, while under the dim illumination condition, the mode of inheritance was dominant for male mice but variable for female mice. The sex differences in mode of inheritance were possibly due to different adaptive functions of the elimination response under the two conditions of illumination. Elimination under bright illumination was possibly related primarily to emotionality, while elimination under dim illumination was possibly related to both emotionality and territorial marking.

scholarly journals Androgen sulphate formation in male and female mice

1969 ◽  
Vol 115 (3) ◽  
pp. 489-493
Author(s):  
D A Lewis
Keyword(s):  
Sex Differences ◽  
Sulphuric Acid ◽  
Female Rats ◽  
Dehydroepiandrosterone Sulphate ◽  
Male And Female ◽  
Female Mice ◽  
Liver Slices ◽  
Rats And Mice

1. After the administration of large doses of androsterone, epiandrosterone, dehydroepiandrosterone and testosterone to mice, females excreted more of the dose conjugated with sulphuric acid than did males. 2. Liver slices from female mice conjugated androgens with sulphuric acid to a greater extent than did slices from males. 3. Sulphotransferase preparations from livers of female rats and mice catalysed the formation of dehydroepiandrosterone sulphate at a faster rate than preparations from livers of the male animals. 4. A possible explanation for the observed sex differences is discussed.

scholarly journals NPY Deficiency Prevents Postmenopausal Adiposity by Augmenting Estradiol-Mediated Browning

2018 ◽  
Vol 75 (6) ◽  
pp. 1042-1049
Author(s):  
Seongjoon Park ◽  
Erkhembayar Nayantai ◽  
Toshimitsu Komatsu ◽  
Hiroko Hayashi ◽  
Ryoichi Mori ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Fat Metabolism ◽  
Male Mice ◽  
Wild Type ◽  
Male And Female ◽  
Female Mice ◽  
Age Related ◽  
Promising Target ◽  
Intracellular Mechanism

Abstract The orexigenic hormone neuropeptide Y (NPY) plays a pivotal role in the peripheral regulation of fat metabolism. However, the mechanisms underlying the effects of sex on NPY function have not been extensively analyzed. In this study, we examined the effects of NPY deficiency on fat metabolism in male and female mice. Body weight was slightly decreased, whereas white adipose tissue (WAT) mass was significantly decreased as the thermogenic program was upregulated in NPY-/- female mice compared with that in wild-type mice; these factors were not altered in response to NPY deficiency in male mice. Moreover, lack of NPY resulted in an increase in luteinizing hormone (LH) expression in the pituitary gland, with concomitant activation of the estradiol-mediated thermogenic program in inguinal WAT, and alleviated age-related modification of adiposity in female mice. Taken together, these data revealed a novel intracellular mechanism of NPY in the regulation of fat metabolism and highlighted the sexual dimorphism of NPY as a promising target for drug development to reduce postmenopausal adiposity.

scholarly journals Gender differences in the response of CD-1 mouse bone to parathyroid hormone: potential role of IGF-I

2006 ◽  
Vol 189 (2) ◽  
pp. 279-287 ◽  
Author(s):  
Yongmei Wang ◽  
Takeshi Sakata ◽  
Hashem Z Elalieh ◽  
Scott J Munson ◽  
Andrew Burghardt ◽  
...  
Keyword(s):  
Gender Differences ◽  
Parathyroid Hormone ◽  
Cortical Bone ◽  
Mineral Apposition Rate ◽  
Mrna Levels ◽  
Male Mice ◽  
Bone Formation Rate ◽  
Male And Female ◽  
Female Mice ◽  
Igf I

Parathyroid hormone (PTH) exerts both catabolic and anabolic actions on bone. Studies on the skeletal effects of PTH have seldom considered the effects of gender. Our study was designed to determine whether the response of mouse bone to PTH differed according to sex. As a first step, we analyzed gender differences with respect to bone mass and structural properties of 4 month old PTH treated (80 μg/kg per day for 2 weeks) male and female CD-1 mice. PTH significantly increased fat free weight/body weight, periosteal bone formation rate, mineral apposition rate, and endosteal single labeling surface, while significantly decreasing medullary area in male mice compared with vehicle treated controls, but induced no significant changes in female mice. We then analyzed the gender differences in bone marrow stromal cells (BMSC) isolated from 4 month old male and female CD-1 mice following treatment with PTH (80 μg/kg per day for 2 weeks). PTH significantly increased the osteogenic colony number and the alkaline phosphatase (ALP) activity (ALP/cell) by day 14 in cultures of BMSCs from male and female mice. PTH also increased the mRNA level of receptor activator of nuclear factor κB ligand in the bone tissue (marrow removed) of both females and males. However, PTH increased the mRNA levels of IGF-I and IGF-IR only in the bones of male mice. Our results indicate that on balance a 2-weeks course of PTH is anabolic on cortical bone in this mouse strain. These effects are more evident in the male mouse. These differences between male and female mice may reflect the greater response to PTH of IGF-I and IGF-IR gene expression in males enhancing the anabolic effect on cortical bone.

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