Extragonadal effects of luteinizing hormone in mice

1989 ◽  
Vol 121 (4) ◽  
pp. 587-594 ◽  
Author(s):  
Kaoru Nomura ◽  
David W. Puett ◽  
David Puett ◽  
Kazuo Shizume ◽  
Grant W. Liddle
Keyword(s):  
Physiological Role ◽  
Male Mice ◽  
Intact Female ◽  
Intact Male ◽  
Kidney Weight ◽  
Kidney Size ◽  
Female Mice ◽  
Cellular Hypertrophy ◽  
Kidney Growth

Abstract. LH is composed of isoforms which exhibit microheterogeneity. We recently demonstrated that a particular ovine or porcine LH preparation (G100-fr.3) stimulates kidney growth. This study was conducted to clarify the physiological role of this renotropic activity and other extragonadal effects of the ovine LH preparation in CD-1 mice. Hypophysectomy caused a significantly greater reduction in relative dry kidney weight (i.e. g/100 g body weight) when compared to adrenalectomy, castration, thyroidectomy, and castration plus thyroidectomy. Supplementation with G100-fr.3 in these animals partially restored not only kidney size but also DNA, RNA and protein content. Treatment with standard LH preparations (NIDDKoLH24 and G3-268DA), as well as PRL, GH, FSH and TSH, failed to reverse the renal atrophy induced by hypophysectomy and castration. Administration of testosterone to castrated hypophysectomized mice increased kidney weight and RNA content, but not renal DNA. The relative dry kidney weight increased significantly at the onset of puberty in intact male mice, but not in castrated males or intact female mice. In addition, human CG increased kidney size in hypophysectomized male mice, but not in castrated hypophysectomized animals. These findings indicate that LH isoforms may regulate kidney growth in the male mouse both directly as a renotropin stimulating hyperplasia and indirectly as a gonadotropin via testicular androgen, producing cellular hypertrophy. It was also noted that G100-fr.3 decreased hepatic weight, DNA, RNA and protein, but produced no significant change in the spleen, heart or adrenal glands in castrated-hypophysectomized mice. Such extragonadal effects of G100-fr.3 were also observed in intact female mice. These results suggest that certain LH isoforms may have extragonadal actions involving the kidney and liver.

Sex-related differences in renal size in mice: ontogeny and influence of neonatal androgens

1987 ◽  
Vol 115 (2) ◽  
pp. 241-246 ◽  
Author(s):  
Ch. Jean-Faucher ◽  
M. Berger ◽  
Ch. Gallon ◽  
M. de Turckheim ◽  
G. Veyssière ◽  
...  
Keyword(s):  
Adult Male ◽  
Cyproterone Acetate ◽  
Growth Response ◽  
Male Mice ◽  
Renal Growth ◽  
Kidney Size ◽  
Female Mice ◽  
Cellular Hypertrophy ◽  
Renal Size ◽  
Androgen Levels

ABSTRACT Kidneys of adult male mice are larger than those of females because of both cellular hyperplasia and hypertrophy. Administration of testosterone to adult female mice induced cellular hypertrophy but not hyperplasia, so that the weight of the kidney remained smaller than in male mice. The sexual dimorphism in kidney size is not congenital but programmed by neonatal endogenous androgens and expressed between 30 and 40 days of age. Treatment of newborn males with cyproterone acetate and of newborn females with testosterone induced female and male patterns of renal growth respectively. It appears that neonatal endogenous androgens are required to induce the characteristic cellular hyperplasia of the kidneys of male mice. Manipulation of androgen levels during neonatal and prepubertal life was found to affect the growth response of the kidney to androgens in adult male and female mice. J. Endocr. (1987) 115, 241–246

Membrane estrogen receptor α is essential for estrogen signaling in the male skeleton

2018 ◽  
Vol 239 (3) ◽  
pp. 303-312 ◽  
Author(s):  
H H Farman ◽  
K L Gustafsson ◽  
P Henning ◽  
L Grahnemo ◽  
V Lionikaite ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptor Α ◽  
Estrogen Signaling ◽  
Areal Bone Mineral Density ◽  
Male Mice ◽  
Mineral Density ◽  
Intact Male ◽  
Trabecular Thickness ◽  
Total Body

The importance of estrogen receptor α (ERα) for the regulation of bone mass in males is well established. ERα mediates estrogenic effects both via nuclear and membrane-initiated ERα (mERα) signaling. The role of mERα signaling for the effects of estrogen on bone in male mice is unknown. To investigate the role of mERα signaling, we have used mice (Nuclear-Only-ER; NOER) with a point mutation (C451A), which results in inhibited trafficking of ERα to the plasma membrane. Gonadal-intact male NOER mice had a significantly decreased total body areal bone mineral density (aBMD) compared to WT littermates at 3, 6 and 9 months of age as measured by dual-energy X-ray absorptiometry (DEXA). High-resolution microcomputed tomography (µCT) analysis of tibia in 3-month-old males demonstrated a decrease in cortical and trabecular thickness in NOER mice compared to WT littermates. As expected, estradiol (E2) treatment of orchidectomized (ORX) WT mice increased total body aBMD, trabecular BV/TV and cortical thickness in tibia compared to placebo treatment. E2 treatment increased these skeletal parameters also in ORX NOER mice. However, the estrogenic responses were significantly decreased in ORX NOER mice compared with ORX WT mice. In conclusion, mERα is essential for normal estrogen signaling in both trabecular and cortical bone in male mice. Increased knowledge of estrogen signaling mechanisms in the regulation of the male skeleton may aid in the development of new treatment options for male osteoporosis.

305 OPTIMIZING DONOR AND RECIPIENT FACTORS IN XENOGRAFTING OF TESTIS TISSUE

2010 ◽  
Vol 22 (1) ◽  
pp. 308
Author(s):  
S. Abbasi ◽  
A. Honaramooz
Keyword(s):  
Recipient Mouse ◽  
Male Mice ◽  
Intact Female ◽  
Intact Male ◽  
Immunodeficient Mice ◽  
Female Nude ◽  
Graft Weight ◽  
And Gender ◽  
Gonadal Status ◽  
Testis Tissue

Grafting of donor mammalian testis tissue into recipient mice allows completion of spermatogenesis in the grafted tissue and therefore can serve as a new option for preservation of male germ line. For testis tissue xenografting, castrated male nude mice typically serve as recipients, each receiving 8 testis tissue fragments; however, no study has comprehensively investigated donor and recipient factors. The objective of this study was to determine the effects of strain of immunodeficient recipient mouse (nude v. SCID), gonadal status (intact v. gonadectomized), and gender (male v. female) on the outcome of testis tissue xenografting. A secondary objective was to determine the optimal number of testis tissue fragments per mouse most suitable for xenografting. Testis parenchyma from newborn piglets were cut into small fragments (5 mg each) and grafted under the back skin of different groups of immunodeficient mice. In Experiment 1, 8 groups of mice (n = 7/group) served as recipients: castrated male nude, intact male nude, ovariectomized female nude, intact female nude, castrated male SCID, intact male SCID, ovariectomized female SCID, and intact female SCID. In Experiment 2, 4 groups of mice (n = 10/group) served as recipients of 2, 4, 8, or 16 testis tissue fragments per mouse. Recipient mice were sacrificed 8 months after grafting and the weight of the grafts and vesicular glands (male mice) were compared among groups by analysis of variance. In Experiment 1, mouse gonadal status (intact v. gonadectomized) did not affect the total graft weight (P > 0.05), but both the recipient mouse strain (nude v. SCID) and gender (male v. female) affected the total graft weight (2460 ± 320.9, 1420 ± 290.0, 758 ± 156.7, and 2780 ± 297.4, mean ± SEM, P < 0.0001 for SCID, nude, female, and male mice, respectively). In Experiment 2, the total graft weight was highest in the group of mice receiving 8 testis tissue fragments (192 ± 76.1, 695 ± 96.5, 2443 ± 338.8, and 1458 ± 305.4, mean ± SEM, P < 0.0001 for 2, 4, 8, or 16 fragment groups, respectively). These results collectively indicate that male SCID mice receiving 8 testis tissue fragments provide optimized conditions for the recovery of largest grafts. Research was supported by grants from the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Saskatchewan Health Research Foundation (SHRF) to A. Honaramooz and scholarships from the Western College of Veterinary Medicine and the International Peace Scholarship to S. Abbasi.

scholarly journals Sex-specific effects of microbiome perturbations on cerebral Aβ amyloidosis and microglia phenotypes

2019 ◽  
Vol 216 (7) ◽  
pp. 1542-1560 ◽  
Author(s):  
Hemraj B. Dodiya ◽  
Thomas Kuntz ◽  
Shabana M. Shaik ◽  
Caroline Baufeld ◽  
Jeffrey Leibowitz ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Amyloid Β ◽  
Fecal Microbiota ◽  
Male Mice ◽  
Female Mice ◽  
Antibiotic Cocktail ◽  
Specific Effects ◽  
Plaque Pathology ◽  
Microglial Morphology

We demonstrated that an antibiotic cocktail (ABX)-perturbed gut microbiome is associated with reduced amyloid-β (Aβ) plaque pathology and astrogliosis in the male amyloid precursor protein (APP)SWE/presenilin 1 (PS1)ΔE9 transgenic model of Aβ amyloidosis. We now show that in an independent, aggressive APPSWE/PS1L166P (APPPS1-21) mouse model of Aβ amyloidosis, an ABX-perturbed gut microbiome is associated with a reduction in Aβ pathology and alterations in microglial morphology, thus establishing the generality of the phenomenon. Most importantly, these latter alterations occur only in brains of male mice, not in the brains of female mice. Furthermore, ABX treatment lead to alterations in levels of selected microglial expressed transcripts indicative of the “M0” homeostatic state in male but not in female mice. Finally, we found that transplants of fecal microbiota from age-matched APPPS1-21 male mice into ABX-treated APPPS1-21 male restores the gut microbiome and partially restores Aβ pathology and microglial morphology, thus demonstrating a causal role of the microbiome in the modulation of Aβ amyloidosis and microglial physiology in mouse models of Aβ amyloidosis.

Role of the ovary in sexual differentiation of lactotrophs and somatotrophs in the mouse adenohypophysis: a stereological morphometric study by electron microscopy

1983 ◽  
Vol 99 (3) ◽  
pp. 355-NP ◽  
Author(s):  
F. Sasaki ◽  
M. Sano
Keyword(s):  
Adult Male ◽  
Sexual Differentiation ◽  
Morphometric Study ◽  
Normal Male ◽  
Corpora Lutea ◽  
Male Mice ◽  
Female Mice ◽  
Pituitary Glands ◽  
Normal Males

To study the effect of the ovary on sexual differentiation of somatotrophs and lactotrophs, the anterior pituitary glands of castrated adult male mice which had received an ovarian transplant during postnatal development were studied using a stereological morphometric technique with an electron microscope. In adult male mice which were castrated neonatally and given ovarian transplants at the age of puberty (NCT-males), the ovaries contained follicles and corpora lutea. The percentages (∼40) and numbers (∼2 × 105) of lactotrophs were similar in normal dioestrous females and NCT-males, but were higher than the percentage (9·3) and number (4·6 × 104) in normal males. Ovarian grafts in adult male mice which were simultaneously castrated and given an ovarian transplant just before puberty (PCT-males) contained numerous follicles of various sizes but no corpora lutea. The percentage (46·8) and number (3·9 × 105) of lactotrophs were greater in these mice than in dioestrous females. The percentage of somatotrophs in NCT-males (34·7) was less than in normal males (52·6), but was similar to that in dioestrous female mice (37·4). The percentage of somatotrophs in PCT-males (27·4) was less than in normal male and dioestrous female mice. These data indicate that lactotrophs and somatotrophs differentiate to the female phenotype when a cyclically functional ovary is present after puberty.

scholarly journals Chronic rapamycin treatment causes diabetes in male mice

2014 ◽  
Vol 307 (4) ◽  
pp. R434-R443 ◽  
Author(s):  
Christine E. Schindler ◽  
Uttara Partap ◽  
Bonnie K. Patchen ◽  
Steven J. Swoap
Keyword(s):  
Glucose Intolerance ◽  
Mammalian Target Of Rapamycin ◽  
Protective Role ◽  
Metabolic Effects ◽  
Current Evidence ◽  
Male Mice ◽  
Rapamycin Treatment ◽  
Female Mice ◽  
Glucose Levels

Current evidence indicates that the mammalian target of rapamycin inhibitor rapamycin both increases longevity and, seemingly contradictorily, impairs glucose homeostasis. Most studies exploring the dimensions of this paradox have been based on rapamycin treatment in mice for up to 20 wk. We sought to better understand the metabolic effects of oral rapamycin over a substantially longer period of time in HET3 mice. We observed that treatment with rapamycin for 52 wk induced diabetes in male mice, characterized by hyperglycemia, significant urine glucose levels, and severe glucose and pyruvate intolerance. Glucose intolerance occurred in male mice by 4 wk on rapamycin and could be only partially reversed with cessation of rapamycin treatment. Female mice developed moderate glucose intolerance over 1 yr of rapamycin treatment, but not diabetes. The role of sex hormones in the differential development of diabetic symptoms in male and female mice was further explored. HET3 mice treated with rapamycin for 52 wk were gonadectomized and monitored over 10 wk. Castrated male mice remained glucose intolerant, while ovariectomized females developed significant glucose intolerance over the same time period. Subsequent replacement of 17β-estradiol (E2) in ovariectomized females promoted a recovery of glucose tolerance over a 4-wk period, suggesting the protective role of E2against rapamycin-induced diabetes. These results indicate that 1) oral rapamycin treatment causes diabetes in male mice, 2) the diabetes is partially reversible with cessation of treatment, and 3) E2plays a protective role against the development of rapamycin-induced diabetes.

scholarly journals Ornithine decarboxylase antizyme in kidneys of male and female mice

1988 ◽  
Vol 254 (2) ◽  
pp. 367-372 ◽  
Author(s):  
Y Murakami ◽  
M Marumo ◽  
S I Hayashi
Keyword(s):  
Ornithine Decarboxylase ◽  
Half Life ◽  
Mouse Kidney ◽  
Repeated Injection ◽  
Male Mice ◽  
Protein Inhibitor ◽  
Male And Female ◽  
Female Mice ◽  
Htc Cells

Antizyme, a protein inhibitor of ornithine decarboxylase (ODC), was shown to be induced in mouse kidney by repeated injection of putrescine. Antizyme was also present as a complex with ODC in the kidney of untreated mouse. The amount of the renal ODC-antizyme complex was 3-fold higher in male mice than in female mice. On the contrary, the proportion of ODC present as a complex with antizyme was 24-fold higher in females than in males, and the decay of renal ODC activity after cycloheximide treatment was about 5-fold more rapid in females than in males. Administration of testosterone to female mice, a procedure known to prolong the half-life of renal ODC, increased both ODC activity and the content of ODC-antizyme complex, but decreased the antizyme/ODC ratio in the kidney. These results are consistent with the previous observation in HTC cells that the decay rate of ODC activity in the presence of cycloheximide correlated well with the proportion of ODC present as a complex with antizyme, suggesting the ubiquitous role of antizyme in ODC degradation.

324 EFFECT OF AGING ON AMOUNTS OF DNA METHYLTRANSFERASE mRNA IN MOUSE SPERMATOZOA

2007 ◽  
Vol 19 (1) ◽  
pp. 277
Author(s):  
H. Kato ◽  
T. Koda ◽  
M. Kishimoto ◽  
T. Mitani ◽  
K. Matsumoto ◽  
...  
Keyword(s):  
Real Time ◽  
Real Time Pcr ◽  
Dna Methyltransferase ◽  
Physiological Role ◽  
Mrna Levels ◽  
Male Mice ◽  
Expression Levels ◽  
Young Males ◽  
Male Age

The spermatozoon is a specially differentiated cell designed to carry a haploid male genome into an oocyte at fertilization. It recently was reported that a matured spermatozoon contains several kinds of mRNAs and these are delivered into the oocyte at fertilization (Ostermeier et al. 2004 Nature 429, 154). The physiological role of paternally derived mRNAs is not clear; however, there is a report that the DNA methyltransferase (Dnmt) mRNA level in spermatozoa from male rats exposed to ethanol was significantly reduced (Bielawski et al. 2002 Alcohl. Clin. Res. 26, 347–351). The reduction of mRNA levels of Dnmt in spermatozoa would lead to altered epigenetic modification of the genome. Because factors such as age may affect spermatozoa mRNA levels, this study evaluated the effect of individual aging on the expression levels of Dnmts during spermatogenesis. This was accomplished by determining expression levels of Dnmts in the whole testis and in spermatozoa from young and aged mice by quantitative reverse-transcription-PCR. Seven- (young) and 68- (aged) week-old C57BL/6N male mice (n = 3/group) were sacrificed by cervical dislocation and whole testes and matured spermatozoa were collected. Total RNA was extracted and purified from each sample. In this study, 5 Dnmts (Dnmt1s, Dnmt1p, Dnmt3a, Dnmt3b, and Dnmt3l) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a reference gene, were examined for expression levels in whole testis and spermatozoa using SYBR Premix Ex Taq (Takara Bio, Inc., Otsu, Shiga, Japan) and the 7300 Real-Time PCR System (Applied Biosystems, Foster City, CA, USA). Real-Time PCR runs for each Dnmt and GAPDH were repeated 3 times using different RNA batches from different individuals. The GAPDH expression level was used to normalize the expression levels of each Dnmt. Data were analyzed by Student&apos;s t-test. Relative expression levels of each Dnmt in testis from aged males compared to that of young males were 0.94, 1.15, 0.91, 1.15, and 1.14 (Dnmt1s, Dnmt1p, Dnmt3a, Dnmt3b, and Dnmt3l, respectively). There was no difference in the expression levels of the 5 Dnmts examined between testes from aged and young males. On the other hand, the relative amounts of each Dnmt mRNA in spermatozoa from aged males compared to that of young males were 0.87, 0.01, 0.54, 1.07, and 1.75 (Dnmt1s, Dnmt1p, Dnmt3a, Dnmt3b, and Dnmt3l, respectively). There was a significant reduction (P &lt; 0.05) in the amount of Dnmt1p mRNA. The reason why the amount of Dnmt1p mRNA in spermatozoa from aged male mice showed such reduction is not clear. There was no difference in the relative expression levels of Dnmt1p in testis irrespective of male age. Dnmt1p is only translated in the spermatocyte during the pachytene stage in meiosis and its physiological role is not clear. To elucidate this male, age-related reduction of the amount of Dnmt1p mRNA in spermatozoa would clarify part of physiological role of Dnmt1p. This work was supported by Wakayama Prefecture Collaboration of Regional Entities for the Advanced of Technological Excellence, Japan, and by a Grant-in-Aid for the 21st Century Center of Excellence Program of the MEXT, Japan.

Abstract P135: 2-methoxyestradiol Minimizes Angiotensin II-induced Hypertension and Renal Dysfunction in Ovariectomized Female and Intact Male Mice

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Ajeeth K Pingili ◽  
Shyamala Thirunavukkarasu ◽  
Nayaab S Khan ◽  
Akemi Katsurada ◽  
Dewan S Majid ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Renal Dysfunction ◽  
Organ Damage ◽  
Ang Ii ◽  
Male Mice ◽  
Intact Male ◽  
Female Mice ◽  
End Organ Damage ◽  
Induced Hypertension ◽  
Post Menopausal

Men and post-menopausal females are more prone to develop hypertension and renal dysfunction as compared to pre-menopausal females. It is well documented that in various experimental models of hypertension, the protection against hypertension in females is lost following ovariectomy (OVX). Recently we have shown that CYP1B1 protects against angiotensin II (Ang II)-induced hypertension and associated cardiovascular changes in female mice, most likely via production of 2-methoxyestradiol (2-ME). This study was conducted to determine if 2-ME reduces Ang II-induced hypertension, renal dysfunction and end organ damage in OVX female, and intact male mice. Treatment of OVX Cyp1b1 +/+ and Cyp1b1 -/- female mice with 2-ME (1.5 mg/kg/day i.p., for 2 weeks) reduced Ang II-induced increase in systolic blood pressure (SBP) (182±5.1 vs. 143± 2.4 mmHg, 179±6.4 vs. 140± 8.6 mmHg, P < 0.05, n= 5), water consumption, urine output and osmolality, and proteinuria (5.5±0.7 vs. 3.3±0.5 mg/24 hrs, 8.4±1.3 vs. 4.4 ±0.9 mg/24 hrs) respectively. 2-ME also reduced Ang II-induced increase in SBP (188±2.6 vs. 143± 2.7 mmHg, P < 0.05, n= 5) in intact male mice. 2-ME did not alter water consumption and urine osmolality, but reduced urine output and sodium excretion, and proteinuria (14.4±2.0 vs. 6.0±0.5 mg/24 hrs) in intact Cyp1b1 +/+ male mice. Treatment with 2-ME attenuated Ang II-induced end-organ damage (actin and collagen accumulation) in OVX Cyp1b1 +/+ and Cyp1b1 -/- female and Cyp1b1 +/+ male mice. 2-ME mitigated urinary excretion of angiotensinogen in OVX Cyp1b1 +/+ and Cyp1b1 -/- female mice infused with Ang II. These data suggest that 2-ME reduces Ang II- induced hypertension and associated renal dysfunction and end-organ damage in OVX Cyp1b1 +/+ and Cyp1b1 -/- female, and intact male mice. Therefore, 2-ME could serve as a therapeutic agent for treatment of hypertension and associated pathogenesis in post-menopausal females, and intact males.

scholarly journals Inducible nitric oxide synthase provides protection against injury-induced thrombosis in female mice

2011 ◽  
Vol 301 (2) ◽  
pp. H617-H624 ◽  
Author(s):  
Rita K. Upmacis ◽  
Hao Shen ◽  
Lea Esther S. Benguigui ◽  
Brian D. Lamon ◽  
Ruba S. Deeb ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Ex Vivo ◽  
Physiological Role ◽  
Thrombotic Occlusion ◽  
Female Mice ◽  
Eicosanoid Production ◽  
Oxide Synthase ◽  
Deficient Mice ◽  
Inducible Nitric Oxide

Nitric oxide (NO) is an important vasoactive molecule produced by three NO synthase (NOS) enzymes: neuronal (nNOS), inducible (iNOS), and endothelial NOS (eNOS). While eNOS contributes to blood vessel dilation that protects against the development of hypertension, iNOS has been primarily implicated as a disease-promoting isoform during atherogenesis. Despite this, iNOS may play a physiological role via the modulation of cyclooxygenase and thromboregulatory eicosanoid production. Herein, we examined the role of iNOS in a murine model of thrombosis. Blood flow was measured in carotid arteries of male and female wild-type (WT) and iNOS-deficient mice following ferric chloride-induced thrombosis. Female WT mice were more resistant to thrombotic occlusion than male counterparts but became more susceptible upon iNOS deletion. In contrast, male mice (with and without iNOS deletion) were equally susceptible to thrombosis. Deletion of iNOS was not associated with a change in the balance of thromboxane A2 (TxA2) or antithrombotic prostacyclin (PGI2). Compared with male counterparts, female WT mice exhibited increased urinary nitrite and nitrate levels and enhanced ex vivo induction of iNOS in hearts and aortas. Our findings suggest that iNOS-derived NO in female WT mice may attenuate the effects of vascular injury. Thus, although iNOS is detrimental during atherogenesis, physiological iNOS levels may contribute to providing protection against thrombotic occlusion, a phenomenon that may be enhanced in female mice.

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