Oestrogen at the neonatal stage is critical for the reproductive ability of male mice as revealed by supplementation with 17beta-oestradiol to aromatase gene (Cyp19) knockout mice

Toda, Katsumi; Okada, Teruhiko; Takeda, Kiyoshi; Akira, Shizuo; Saibara, Toshiji; Shiraishi, M; Onishi, Saburo; Shizuta, Yutaka

doi:10.1677/joe.0.1680455

Cited by 96 publications

(69 citation statements)

References 38 publications

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“…DHT binds to AR with higher affinity, and has two to ten fold higher potency than testosterone in androgen-responsive tissues (8). On the other hand, estrogen plays a major role in regulating metabolic processes (9,10), mood and cognition (11), cardiovascular disease (12,13), sexual function including libido (14), and bone turnover in men (15,16). Testosterone is the major androgen that acts in 'DHT-independent' tissues, such as skeletal muscle, where 5α-reductase is not expressed or expressed at a very low level (17) and it directly regulates skeletal muscle growth, bone formation, fat distribution, and sexual function.…”

Section: Steroidal Ligandsmentioning

confidence: 99%

Pharmacokinetics and Pharmacodynamics of Nonsteroidal Androgen Receptor Ligands

2006

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Testosterone and structurally related anabolic steroids have been used to treat hypogonadism, muscle wasting, osteoporosis, male contraception, cancer cachexia, anemia, and hormone replacement therapy in aging men or age-related frailty; while antiandrogens may be useful for treatment of conditions like acne, alopecia (male-pattern baldness), hirsutism, benign prostatic hyperplasia (BPH) and prostate cancer. However, the undesirable physicochemical and pharmacokinetic properties of steroidal androgen receptor (AR) ligands limited their clinical use. Nonsteroidal AR ligands with improved pharmacological and pharmacokinetic properties have been developed to overcome these problems. This review focuses on the pharmacokinetics, metabolism, and pharmacology of clinically used and emerging nonsteroidal AR ligands, including antagonists, agonists, and selective androgen receptor modulators.

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Section: Steroidal Ligandsmentioning

confidence: 99%

Pharmacokinetics and Pharmacodynamics of Nonsteroidal Androgen Receptor Ligands

2006

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“…The genotypes of the mice were determined by PCR using DNA from tail tips (Toda et al 2001a). Wild-type (+/+) male littermates were used as controls.…”

Section: Micementioning

confidence: 99%

“…ArKO males (second group above) were injected with 7·5 µg E2 every three days for the first 3 weeks after birth and once a week thereafter with 0·75 µg E2 (Toda et al 2001a). In the third group of ArKO mice, E2 (0·75 µg/ mouse) was given every week beginning at 24 weeks of age until 36 weeks of age when ITT and IPGTT studies were carried out.…”

Section: Effects Of Estradiol Bezafibrate and Pioglitazone On Glucosmentioning

confidence: 99%

Progressive development of insulin resistance phenotype in male mice with complete aromatase (CYP19) deficiency

Takeda

Toda²,

Saibara³

et al. 2003

Journal of Endocrinology

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165

121

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Aromatase (CYP19) is a cytochrome P450 enzyme that catalyzes the formation of aromatic C18 estrogens from C19 androgens. It is expressed in various tissues and contributes to sex-specific differences in cellular metabolism. We have generated aromatase-knockout (ArKO) mice in order to study the role of estrogen in the regulation of glucose metabolism. The mean body weights of male ArKO ( / ) mice (n=7) and wild-type littermates (+/+) (n=7) at 10 and 12 weeks of age were 26·7 1·9 g vs 26·1 0·8 g and 28·8 1·4 g vs 26·9 1·0 g respectively. The body weights of the ArKO and wild-type mice diverged between 10 and 12 weeks of age with the ArKO males weighing significantly more than their wild-type littermates (P<0·05). The ArKO males showed significantly higher blood glucose levels during an intraperitoneal glucose tolerance test compared with wild-type littermates beginning at 18 weeks of age. By 24 weeks of age, they had higher fasting blood glucose levels compared with wild-type littermates (133·8 22·8 mg/dl vs 87·8 20·3 mg/dl respectively; P<0·01). An intraperitoneal injection of insulin (0·75 mU insulin/g) caused a continuous decline in blood glucose levels in wild-type mice whereas ArKO males at 18 weeks and older exhibited a rebound increase in glucose levels 30 min after insulin injection. Thus, ArKO male mice appear to develop glucose intolerance and insulin resistance in an age-dependent manner. There was no difference in fasting serum triglyceride and total cholesterol levels between ArKO male mice and wild-type littermates at 13 and 25 weeks of age. However, serum triglyceride and cholesterol levels were significantly elevated following a meal in ArKO mice at 36 weeks of age. Serum testosterone levels in ArKO male mice were continuously higher compared with wild-type littermates. Treatment of ArKO males with 17 -estradiol improved the glucose response as measured by intraperitoneal glucose and insulin tolerance tests. Treatment with fibrates and thiazolidinediones also led to an improvement in insulin resistance and reduced androgen levels. As complete aromatase deficiency in man is associated with insulin resistance, obesity and hyperlipidemia, the ArKO mouse may be a useful animal model for examining the role of estrogens in the control of glucose and lipid homeostasis.

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“…Male mice null for aromatase have profound deficits in mating and aggression (Table 2) (Honda et al, 1998;Matsumoto et al, 2003;Toda et al, 2001a;Toda et al, 2001b). In a standard mating assay, these mutant males mount a female less frequently than wildtype males, exhibit reductions in intromissions, and rarely ejaculate.…”

Section: The Role Of Estrogen Signaling In Male Mating and Aggressionmentioning

confidence: 99%

A genetic approach to dissect sexually dimorphic behaviors

Juntti

Coats

Shah

2008

Hormones and Behavior

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It has been known since antiquity that gender-specific behaviors are regulated by the gonads. We now know that testosterone is required for the appropriate display of male patterns of behavior. Estrogen and progesterone, on the other hand, are essential for female typical responses. Research from several groups also indicates that estrogen signaling is required for male typical behaviors. This finding raises the issue of the relative contribution of these two hormonal systems in the control of male typical behavioral displays. In this review we discuss the findings that led to these conclusions and suggest various genetic strategies that may be required to understand the relative roles of testosterone and estrogen signaling in the control of gender specific behavior.All animals exhibit sex differences in behavior that are characteristic of the species. Such gender typical behaviors are often used to court mates, to defend territory and other resources, and to procure food for mates and offspring. These sexual dimorphisms in behavior are often innate and can be displayed without prior social experience or training, suggesting that the neural circuits that mediate these behaviors are developmentally hardwired in the brain. Nevertheless, the display of these behaviors is tightly regulated by external sensory cues as well as internal physiological regulators such as hormones. Such dual control ensures that animals engage in these behaviors only at the appropriate time and circumstance. While we have learned much about the sensory and hormonal control of sexually dimorphic behaviors (Morris et

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Oestrogen at the neonatal stage is critical for the reproductive ability of male mice as revealed by supplementation with 17beta-oestradiol to aromatase gene (Cyp19) knockout mice

Cited by 96 publications

References 38 publications

Pharmacokinetics and Pharmacodynamics of Nonsteroidal Androgen Receptor Ligands

Pharmacokinetics and Pharmacodynamics of Nonsteroidal Androgen Receptor Ligands

Progressive development of insulin resistance phenotype in male mice with complete aromatase (CYP19) deficiency

A genetic approach to dissect sexually dimorphic behaviors

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