Altering rat sexual behavior to teach hormonal regulation of brain imprinting

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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62 Altering sexual behavior of rats through neonatal treatment with an aromatase inhibitor, estrogen receptor antagonist and testosterone

Journal of Animal Science ◽

10.1093/jas/skaa054.261 ◽

2020 ◽

Vol 98 (Supplement_3) ◽

pp. 148-149

Author(s):

Sara K Gholson ◽

Amanda Schmelzle ◽

Jonathon Green ◽

Micheal Smith ◽

Rodney Geisert

Keyword(s):

Estrogen Receptor ◽

Body Weight ◽

Sexual Behavior ◽

Aromatase Inhibitor ◽

Receptor Antagonist ◽

Litter Size ◽

Accessory Gland ◽

Mammalian Brain ◽

Estrogen Receptor Antagonist ◽

The Brain

Abstract The mammalian brain is sexually dimorphic until becoming imprinted before birth or during neonatal development. The naïve mammalian brain of neonates is programmed to become feminine. In male neonates, testosterone crosses the blood brain barrier where it is converted to estrogen by aromatase. Estrogen in the brain imprints male sexual behavior. In female neonates, estrogen binds to alpha fetoprotein which prohibits estrogen from entering the brain. The present study was undertaken to determine if testosterone, an estrogen receptor antagonist (ICI 182,780) or aromatase inhibitor (Letrozole) would alter sexual behavior in neonatal rats. In this study, the entire litter of neonatal rat pups received a sc injection (100µl) of one of the following four treatments: corn oil (CO), testosterone propionate 100 µg (TP), ICI 182,780 100 µg (ICI), or Letorozole 100 µg (LET) on days 1 and 3 after birth. At approximately 60-70 days of age, treated rats were placed in cages with nontreated rats of the opposite sex. Animals were euthanized after 20 days. Body, testis, epididymal, and accessory gland weights were recorded for males as well as the number of females they bred and litter size. Body weight, pregnancy status, and litter size (if pregnant) were recorded for treated females. While there was a difference (P< 0.001) in body weight between males and females (average 372 g vs 279 g respectively), there was no statistical differences in body, testis, epididymal, or accessory gland weight between male treatment groups. While number of females pregnant or litter size was not different for CO, TP, or ICI, LET males established no pregnancies. Body weight, number pregnant and litter size were not different between female CO, ICI, or LET treatments. However, TP treated females established no pregnancies. Sexual mating behavior is altered by neonatal exposure to an aromatase inhibitor or testosterone in rats.

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A new mechanism of estrogen action in prostate cancer: Inhibition of tissue androgen production and prostate cancer growth by Estradiol in androgen independent prostate cancer xenografts

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.15509 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 15509-15509

Author(s):

B. Montgomery ◽

P. Nelson ◽

D. L. Hess ◽

R. Vessella ◽

E. Corey

Keyword(s):

Prostate Cancer ◽

Estrogen Receptor ◽

Tumor Growth ◽

Receptor Antagonist ◽

Human Prostate ◽

Human Prostate Cancer ◽

Ici 182,780 ◽

Estrogen Receptor Antagonist ◽

Serum Androgens ◽

Androgen Independent

15509 Background: Estrogens are effective agents in treating prostate cancer in patients in which serum androgens are already at ‘castrate‘ or anorchid levels. The mechanisms whereby estrogens inhibit ‘androgen-independent‘ prostate cancer are unclear. Methods: The androgen-independent human prostate cancer xenograft LuCaP 35V was implanted into orchiectomized male SCID mice and established tumors were treated with placebo pellets, 17β-estradiol (E2) slow-release pellets or E2 with the estrogen receptor antagonist ICI 182,780 as previously described (Clin Cancer Res 8:1003). Effects of E2 on tumor growth and tissue testosterone (T) and dihydrotestosterone (DHT) levels were evaluated by radioimmunoassay. Results: E2 significantly inhibited growth of androgen-independent LuCaP35V ( ∼35% inhibition at 4 weeks, p=0.0047, and increased survival of tumor bearing animals, (p trend =0.03) . The estrogen receptor antagonist ICI 182,780 did not block E2 inhibition of tumor growth, suggesting a receptor independent mechanism of tumor suppression. We then examined the effect of E2 on tissue T and DHT. E2 suppressed levels of tumor T and DHT in treated tumors. Tissue androgens in placebo treated LuCaP35V xenografts were; T=1.21 (± 0.18) pg/mg and DHT=3.54 (±1.07) pg/mg, and in E2-treated LuCaP35V T=0.23 (±0.09) pg/mg and DHT =0.44 (±0.14) pg/mg, (p<0.001). Levels of T and DHT in control liver tissue from both placebo and E2-treated animals were equivalent, at less than 0.2 pg/mg. Conclusions: We have shown that E2 inhibits growth of the androgen- independent human prostate cancer xenograft LuCaP35V, and that this inhibition is estrogen receptor independent. E2 significantly suppressed tumor tissue T and DHT suggesting a new mechanism of E2 mediated growth inhibition of androgen independent prostate cancer, potentially through inhibition of tumoral steroidogenesis. This model of ‘intracrine‘ tumor androgen production can be used to evaluate other inhibitors of tissue steroidogenesis. No significant financial relationships to disclose.

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Disinhibition of female sexual behavior by a CRH receptor antagonist in Syrian hamsters

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00233.2002 ◽

2002 ◽

Vol 283 (3) ◽

pp. R591-R597 ◽

Cited By ~ 20

Author(s):

Juli E. Jones ◽

Rebecca R. Pick ◽

Matthew D. Davenport ◽

Alex C. Keene ◽

Eric S. Corp ◽

...

Keyword(s):

Sexual Behavior ◽

Receptor Antagonist ◽

Direct Evidence ◽

Sexual Receptivity ◽

Receptor Signaling ◽

Common Pathway ◽

Female Sexual Behavior ◽

Central Actions ◽

The Brain ◽

Estrous Behavior

Several conditions that inhibit female sexual behavior are thought to be associated with altered corticotropin-releasing hormone (CRH) activity in the brain. The present experiments examined the hypothesis that endogenous CRH receptor signaling mediates the inhibition of estrous behavior by undernutrition and in other instances of sexual dysfunction. Intracerebroventricular (ICV) infusion of CRH or urocortin inhibited estrous behavior in ovariectomized steroid-primed hamsters. Conversely, ICV infusion of the CRH receptor antagonist astressin prevented the suppression of estrous behavior by food deprivation or by ICV administration of neuropeptide Y. Astressin treatment also induced sexual receptivity in nonresponders, animals that do not normally come into heat when treated with hormones, and this effect persisted in subsequent weekly tests in the absence of any further astressin treatment. Activation of the hypothalamo-pituitary-adrenocortical axis was neither necessary nor sufficient to inhibit estrous behavior, indicating that this phenomenon is due to other central actions of CRH receptor agonists. This is the first direct evidence that CRH receptor signaling may be a final common pathway by which undernutrition and other conditions inhibit female sexual behavior.

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