Gender Differences in the Membrane Transport of Endogenous and Exogenous Compounds

Morris, Marilyn E.; Lee, Hwa Jeong; Predko, Lisa

doi:10.1124/pr.55.2.1

Cited by 119 publications

(80 citation statements)

References 82 publications

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“…Note that these adverse effects were not detected in female animals [see Supplemental Information: "Subchronic Toxicity Report" in Mruk et al (2006)]. Although a reason for this has yet to be determined, gender differences that are in part under hormonal control can affect the ability of some organs, such as the liver, to metabolize certain drugs (Morris et al, 2003). Taken collectively, these results illustrate that the margin between safety and efficacy would have to be widened significantly in order for adjudin to become a male contraceptive for human use.…”

Section: Acute and Subchronic Toxicitymentioning

confidence: 99%

Anchoring Junctions As Drug Targets: Role in Contraceptive Development

2008

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Section: Acute and Subchronic Toxicitymentioning

confidence: 99%

Anchoring Junctions As Drug Targets: Role in Contraceptive Development

2008

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“…This sexual dimorphism can affect the distribution of highly lipophilic drugs, and therefore influence analgesic drug potency, efficacy, and duration of action. Other aspects of pharmacokinetics, including liver metabolism and membrane transport, may differ between the sexes [139,144], possibly affecting analgesic potency, efficacy, and duration of action.Immune responses also differ between the sexes [21], which may contribute to sex differences in response to chronic inflammatory and neuropathic pain. The activity level of female rodents varies dramatically across the estrous cycle [24,74], which may introduce a confound on pain tests that allow subjects to locomote freely, such as the hot-plate test.…”

mentioning

confidence: 99%

Studying sex and gender differences in pain and analgesia: A consensus report

Greenspan

Craft

LeResche

et al. 2007

Pain

871

633

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In September 2006, members of the Sex, Gender and Pain Special Interest Group of the International Association for the Study of Pain met to discuss the following: (1) what is known about sex and gender differences in pain and analgesia; (2) what are the "best practice" guidelines for pain research with respect to sex and gender; and (3) what are the crucial questions to address in the near future? The resulting consensus presented herein includes input from basic science, clinical and psychosocial pain researchers, as well as from recognized experts in sexual differentiation and reproductive endocrinology. We intend this document to serve as a utilitarian and thought-provoking guide for future research on sex and gender differences in pain and analgesia, both for those currently working in this field as well as those still wondering, "Do I really need to study females?" Keywords Sex differences; Gonadal hormones; Estrogens The case for studying sex and gender differences in pain and analgesiaThe pain field has moved from debating whether sex differences in pain exist to recognizing the importance of these differences. Attention is now directed toward understanding (1) what conditions lead to the expression of sex and gender differences in pain experience and reactivity, (2) what mechanisms underlie these differences, and (3) how these differences can inform clinical management of pain.As noted in a recent review, at least 79% of animal studies published in Pain over the preceding 10 years included male subjects only, with a mere 8% of studies on females only, and another 4% explicitly designed to test for sex differences (the rest did not specify) [142]. Given the substantially greater prevalence of many clinical pain conditions in women vs. men [20,199], and growing evidence for sex differences in sensitivity to experimental pain and to analgesics [21,41,213], we recommend that all pain researchers consider testing their hypotheses in both sexes, or if restricted by practical considerations, only in females. It is invalid to assume that data obtained in male subjects will generalize to females, and the best non-human model of the modal human pain sufferer -a woman -is a female animal. If only males are examined in a given study, it is important that a rationale for exclusion of females be provided and that the potential limitation in generalizability of the findings be addressed in the discussion, particularly when examining a pain phenomenon that occurs with greater prevalence or severity in females. In both preclinical and clinical studies, a comparison of both sexes will further our understanding of individual differences in sensitivity to pain and analgesia, thus improving our ability to treat and prevent pain in all people. General considerationsTwo issues of terminology are important. First, the term "sex" refers to biologically based differences, while the term "gender" refers to socially based phenomena. Although biological sex exerts a major influence on one's gender identity, sex and gender a...

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“…This observation corresponds to that of the laborious method in rats observed by Brommaga et al 34) , in which intestinal calcium absorption in OVX rats was identical to the mean value for the estrous cycling rats. Morris et al 31) and Song et al 32,33) also reported gender-related differential intestinal calcium absorption.…”

Section: Discussionmentioning

confidence: 94%

“…Although ALP is a marker related to liver function, ALP also is indicative of bone resorption and bile duct function. The increases in serum electrolyte concentration in OVX mice were also relatively small compared with that of SHAM mice, and therefore indicated that electrolyte balance was regulated by renal function to maintain homeostatic normal ranges 31,32) . The increase in renal function may indicate that the kidney balances serum electrolytes to a normal level by retaining electrolytes or other elements.…”

Section: Characterization Of Ovx Micementioning

confidence: 99%

Effects of Hachimi-jio-gan Extract on Intestinal Absorption of Calcium in Ovariectomized Mice and Stimulation of RANKL-induced Osteoclast Differentiation of Raw264.7 Cells by Lipopolysaccharide

Ueda

Kanayama

Yamauchi

et al. 2012

J. Hard Tissue Biology.

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: Osteoporosis is a common metabolic bone disease often affecting postmenopausal women, and various medicines are available that attempt to treat and/or prevent this disease. Hachimi-jio-gan is a traditional oriental (Kampo) medicine used clinically, but it's mode of action is still unknown. In this study, the effects of Hachimi-jio-gan extract on intestinal calcium absorption were evaluated in an osteoporosis model using ovariectomized (OVX) and sham-operated (SHAM) mice by investigating pharmacokinetic parameters in these animals. The ability of Hachimi-jio-gan extract to inhibit lipopolysaccharide-mediated stimulation of osteoclasts in bones using receptor activator of the NF-kB ligand (RANKL)-induced osteoclast differentiation of RAW264.7 cells was also investigated. The metabolic behavior of calcium did not differ between OVX and SHAM mice as the pharmacokinetics of calcium was equivalent after intravenous administration. The absolute bioavailability of calcium indicated that the extent of intestinal calcium absorption in the OVX (10.3%) and SHAM (10.7%) mice was at similar low levels. Hachimi-jio-gan extract potentially improved the intestinal calcium absorption by 1.96-and 1.86-fold, respectively. Hachimi-jio-gan extract further suppressed the potent stimulation of RANKL-induced osteoclast differentiation in RAW264.7 cells. These results suggest that Hachimi-jio-gan extract may be suitable for treatment and prevention of osteoporosis through its ability to increase intestinal calcium absorption and suppress osteoclast differentiation.

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Gender Differences in the Membrane Transport of Endogenous and Exogenous Compounds

Cited by 119 publications

References 82 publications

Anchoring Junctions As Drug Targets: Role in Contraceptive Development

Anchoring Junctions As Drug Targets: Role in Contraceptive Development

Studying sex and gender differences in pain and analgesia: A consensus report

Effects of Hachimi-jio-gan Extract on Intestinal Absorption of Calcium in Ovariectomized Mice and Stimulation of RANKL-induced Osteoclast Differentiation of Raw264.7 Cells by Lipopolysaccharide

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