Estrogen receptor 2b is the major determinant of sex-typical mating behavior and sexual preference in medaka

In this teaching laboratory, students design and perform an experiment to determine estrogen’s role in imprinting the brain of neonatal rats to express either male or female sexual behavior. A discussion question is provided before the laboratory exercise in which each student is asked to search the literature and provide written answers to questions and to formulate an experiment to test the role of estrogen in imprinting the mating behavior of male and female rats. Students discuss their answers to the questions in laboratory with the instructor and design an experiment to test their hypothesis. In male rats, testosterone is converted by aromatase expressed by neurons in the brain to estrogen. Production of estrogen in the brain of neonatal rats imprints mating behavior in males, where a lack of estrogen action in the brain imprints female sexual behavior. The model involves administering exogenous testosterone to imprint male behavior in female pups or administration of an aromatase inhibitor (letrozole) or an estrogen receptor antagonist (ICI 182,780) to imprint female sexual behavior in male pups. In the model, litters of neonatal pups are treated with either carrier (control), testosterone propionate, aromatase inhibitor (letrozole), or an estrogen receptor antagonist (ICI 182,780) postnatally on days 1 and 3. Alteration of mating behavior is evaluated through the numbers of males and females that breed and establish pregnancy. This is a very simple protocol that provides an excellent experiment for student discussion on the effects of hormone action on imprinting brain sexual behavior.

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LHRH and mating behavior: Sexual receptivity versus sexual preference

Pharmacology Biochemistry and Behavior ◽

10.1016/0091-3057(85)90304-1 ◽

1985 ◽

Vol 22 (6) ◽

pp. 967-972 ◽

Cited By ~ 21

Author(s):

Carol A. Dudley ◽

Robert L. Moss

Keyword(s):

Mating Behavior ◽

Sexual Preference ◽

Sexual Receptivity

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Direct Repression of FLIP Expression by c-myc Is a Major Determinant of TRAIL Sensitivity

Molecular and Cellular Biology ◽

10.1128/mcb.24.19.8541-8555.2004 ◽

2004 ◽

Vol 24 (19) ◽

pp. 8541-8555 ◽

Cited By ~ 171

Author(s):

M. Stacey Ricci ◽

Zhaoyu Jin ◽

Michael Dews ◽

Duonan Yu ◽

Andrei Thomas-Tikhonenko ◽

...

Keyword(s):

Estrogen Receptor ◽

Tumor Cell ◽

Cell Lines ◽

Death Receptor ◽

Major Determinant ◽

Luciferase Reporter ◽

Tnf Α ◽

Significant Difference ◽

Trail Sensitivity ◽

Resistant Cells

ABSTRACT Tumor necrosis factor alpha (TNF-α)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF-α family of death receptor ligands and holds great therapeutic potential as a tumor cell-specific cytotoxic agent. Using a panel of established tumor cell lines and normal cells, we found a significant difference between the number of TRAIL-sensitive cells expressing high levels of c-myc and TRAIL-resistant cells expressing low levels of c-myc (P < 0.05, n = 19). We also found a direct linear correlation between c-myc levels and TRAIL sensitivity in TRAIL-sensitive cell lines (r = 0.94, n = 6). Overexpression of c-myc or activation of a myc-estrogen receptor (ER) fusion sensitized TRAIL-resistant cells to TRAIL. Conversely, small interfering RNA (siRNA)-mediated knockdown of c-myc significantly reduced both c-myc expression and TRAIL-induced apoptosis. The gene encoding the inhibitor of caspase activation, FLICE inhibitory protein (FLIP), appears to be a direct target of c-myc-mediated transcriptional repression. Overexpression of c-myc or activation of myc-estrogen receptor (ER) decreased FLIP levels both in cell culture and in mouse models of c-myc-induced tumorigenesis, while knocking down c-myc using siRNA increased FLIP expression. Chromatin immunoprecipitation and luciferase reporter analyses showed that c-myc binds and represses the human FLIP promoter. c-myc expression enhanced TRAIL-induced caspase 8 cleavage and FLIP cleavage at the death-inducing signaling complex. Combined siRNA-mediated knockdown of FLIP and c-myc resensitized cells to TRAIL. Therefore, c-myc down-regulation of FLIP expression provides a universal mechanism to explain the ability of c-myc to sensitize cells to death receptor stimuli. In addition, identification of c-myc as a major determinant of TRAIL sensitivity provides a potentially important screening tool for identification of TRAIL-sensitive tumors.

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