Gender differences in drug metabolism regulated by growth hormone

Shapiro, Barry A.; Agrawal, Arun K.; Pampori, Nisar A.

doi:10.1016/1357-2725(94)00056-5

Cited by 215 publications

(193 citation statements)

References 54 publications

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“…As expected [11,12], we observed a profound sexual dimorphism in hepatic CYP2C11 mRNA in which concentrations in intact female liver were <0.2% of that in intact male liver (Table 1); explaining why studies using less sensitive assays than quantitative real-time PCR report undetectable levels of the isoform in female rat liver [10,11]. Although not as dramatic as what could be characterized as the "male-specificity" of CYP2C11 mRNA in liver; spleen and bone marrow exhibited a "male-predominance" in transcript levels in intact rats.…”

Section: Sexually Dimorphic Expression Of Cyp2c11 In Hematopoietic Tisupporting

confidence: 86%

“…The malespecificity of the hepatic isoform has been widely reported [11,12,24,27]. Although we found no sex differences in thymic CYP2C11 in intact rats, there was a substantial sexual dimorphism in the spleen (M:F, 2:1) and bone marrow (M:F, 8:1).…”

Section: Discussionsupporting

confidence: 42%

“…of recombinant rat GH (National Hormone and Peptide Program and Dr. A.F. Parlow, Harbor-UCLA Medical Center, Torrance, CA) by an external syringe pump apparatus over a 3 min period with a frequency of 6 pulses per day (i.e., one pulse every 4hr) for a total of 14 pulses to replicate the physiologic masculine circulating GH profile [12,14]. Control rats were similarly infused with vehicle.…”

Section: Surgical Implantation Of Catheters Gh Treatment and Assaymentioning

confidence: 99%

“…2) exhibited typical sexually dimorphic GH profiles [10,12,15]. Intact males secreted GH in episodic bursts (~250 ng/ml of plasma) about every 3.5-4h.…”

Section: Renaturalization Of the Circulating Episodic Rat Gh Profilementioning

confidence: 99%

“…Accordingly, in the present study we have examined lymphatic tissues for the presence of CYP2C11. Moreover, since hepatic expression of the isoform is sexually dimorphic due to sex-differences in the circulating GH profiles, i.e., episodic for males, continuous-like for females [11,12], we compared splenic, thymic and bone marrow CYP2C11 levels in both male and female rats as well as determined the influence of GH on the sexually dimorphic response of the isoform.…”

Section: Introductionmentioning

confidence: 99%

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Sex-dependent expression of CYP2C11 in spleen, thymus and bone marrow regulated by growth hormone

Thangavel

Dhir

Volgin

et al. 2007

Biochemical Pharmacology

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CYP2C11, the most commonly expressed isoform of cytochrome P450 in male rat liver, was measured in spleen, thymus and bone marrow by quantitative real-time PCR and enhanced Western blotting. CYP2C11 concentrations in the lymphoid tissues were a fraction of that observed in liver, but like the liver, were sexually dimorphic (M>F) with mRNA and protein levels in agreement. Although the response to hypophysectomy varied according to tissue and sex, expression levels of CYP2C11 in all measured tissues remained greater in males. Further differences in CYP2C11 expression between liver and lymphoid tissue were observed following restoration of the circulating masculine growth hormone profile in hypophysectomized rats. In contrast to the liver where the renaturalized growth hormone profile elevated CYP2C11 expression in both sexes, the response was opposite in spleen and thymus with isoform concentrations declining in both sexes. Lastly, the divergent response of CYP2C11 between the liver and immune system was examined in cultured splenocytes exposed to different mitogens. In contrast to the dramatic depletion of CYP2C11 reported in proliferating hepatocytes, mitogen-stimulation resulted in a significant elevation in splenocyte CYP2C11 expression. In summary, we report for the first time that thymus, spleen and bone marrow express, albeit nominal, sex-dependent levels of CYP2C11 (M>F) whose regulation appears to be under some hormonal control, but very different from that of the hepatic isoform.

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Section: Sexually Dimorphic Expression Of Cyp2c11 In Hematopoietic Tisupporting

confidence: 86%

Section: Discussionsupporting

confidence: 42%

Section: Surgical Implantation Of Catheters Gh Treatment and Assaymentioning

confidence: 99%

“…2) exhibited typical sexually dimorphic GH profiles [10,12,15]. Intact males secreted GH in episodic bursts (~250 ng/ml of plasma) about every 3.5-4h.…”

Section: Renaturalization Of the Circulating Episodic Rat Gh Profilementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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