Effects of intrahypothalamic administration of antisense DNA for progesterone receptor mRNA on reproductive behavior and progesterone receptor immunoreactivity in female rat

Ogawa, Sonoko; Olazábal, U.E.; Is, Parhar; Pfaff, D. W.

doi:10.1523/jneurosci.14-03-01766.1994

Cited by 170 publications

(74 citation statements)

References 35 publications

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“…This result confirms recent reports that describe the failure of progesterone to induce a sexual behavioral response in estrogen-primed ovariectomized rats that were previously administered antisense oligonucleotides to the PR intracerebroventrically (Mani et al 1994b) and into the ventromedial hypothalamus (Ogawa et al 1994). Together these results demonstrate that the PR, induced by estrogen in the region of the ventral medial nucleus of the hypothalamus (VMNH) and in the preoptic area, is essential for the expression of this behavioral response.…”

Section: The Pr Is Essential For the Expression Of Lordosissupporting

confidence: 91%

Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities.

Lydon¹,

DeMayo²,

Funk³

et al. 1995

Genes Dev.

1,699

1,242

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Although progesterone has been recognized as essential for the establishment and maintenance of pregnancy, this steroid hormone has been recently implicated to have a functional role in a number of other reproductive events. The physiological effects of progesterone are mediated by the progesterone receptor (PR), a member of the nuclear receptor superfamily of transcription factors. In most cases the PR is induced by estrogen, implying that many of the in vivo effects attributed to progesterone could also be the result of concomitantly administered estrogen. Therefore, to clearly define those physiological events that are specifically attributable to progesterone in vivo, we have generated a mouse model carrying a null mutation of the PR gene using embryonic stem cell/gene targeting techniques. Male and female embryos homozygous for the PR mutation developed normally to adulthood. However, the adult female PR mutant displayed significant defects in all reproductive tissues. These included an inability to ovulate, uterine hyperplasia and inflammation, severely limited mammary gland development, and an inability to exhibit sexual behavior. Collectively, these results provide direct support for progesterone's role as a pleiotropic coordinator of diverse reproductive events that together ensure species survival.

show abstract

Section: The Pr Is Essential For the Expression Of Lordosissupporting

confidence: 91%

Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities.

Lydon¹,

DeMayo²,

Funk³

et al. 1995

Genes Dev.

1,699

1,242

View full text Add to dashboard Cite

show abstract

“…Another aspect of this experiment to consider is the timing of the effects. Based upon previous studies utilizing similar antisense oligonucleotides regimen, protein knockdown occurs between 12 and 48 h following antisense oligonucleotide administration (McCarthy et al, 1994(McCarthy et al, , 2000Ogawa et al, 1994). Although we cannot know that, at the initial time of conditioning of E 2 and ER antisense oligonucleotides (30 min after administration), expression of ERs was knocked down, knockdown of ERs at 24 h is consistent with the actions of E 2 at ERs being blocked by ER antisense oligonucleotides on the second day in the nonpreferred side of the CPP chamber and Western blot analyses.…”

Section: Neuropsychopharmacologymentioning

confidence: 99%

Estradiol-Induced Conditioned Place Preference may Require Actions at Estrogen Receptors in the Nucleus Accumbens

Walf

Rhodes

Meade

et al. 2006

Neuropsychopharmacol

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Intrinsic rewarding effects of estradiol (E 2 ) may underlie some of the sex differences that emerge postpuberty for the prevalence of drug use and behavioral responses to drugs, but the effects and mechanisms of E 2 for reward have not been well characterized. Conditioned place preference (CPP), as measured by the time spent on the nonpreferred/drug-associated side of the chamber, was utilized as a functional assay to investigate the effects and mechanisms of E 2 in the nucleus accumbens for reward. To determine whether intracellular estrogen receptors (ERs) are important for E 2 -induced CPP, rats were administered E 2 (10 mg; subcutaneously (s.c.)), which produced CPP in each experiment, and/or ER blockers, such as tamoxifen (Experiment 1), ICI 182,780 (Experiment 2), or antisense oligonucleotides targeted to ERs (Experiment 3). Experiment 1: E 2 significantly increased the time spent on the originally nonpreferred side of the chamber. Coadministration of tamoxifen (10 mg/kg; s.c.) attenuated effects of E 2 to produce a CPP, but tamoxifen alone, increased time spent on the nonpreferred side. Experiment 2: coadministration of ICI 182,780 (10 mg/ml) to the nucleus accumbens attenuated effects of E 2 to enhance CPP and did not produce a CPP when administered alone. Experiment 3: coadministration of s.c. E 2 with ER antisense oligonucleotides to the nucleus accumbens significantly decreased time spent on the nonpreferred side and expression of ERs in the nucleus accumbens compared to scrambled antisense oligonucleotides or saline vehicle administration. Thus, E 2 's rewarding effects may involve actions at ERs in the nucleus accumbens.

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“…This effect requires the nuclear progesterone receptor (PR), as it disappears after antisense DNA against PR mRNA has been administered onto VMH neurons. [21][22][23] It also disappears in PR knockout mice. 24 Since PR, itself, is a transcription factor, it is induction by E might imply that certain downstream genes would, consequently, be upregulated.…”

mentioning

confidence: 97%

Hormonal symphony: steroid orchestration of gene modules for sociosexual behaviors

Mong

Pfaff

2004

Mol Psychiatry

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Genes induced by estrogens in the mammalian forebrain influence a variety of neural functions. Among them, reproductive behavior mechanisms are very well understood. Their functional genomics provide a theoretical paradigm for linking genes to neural circuits to behavior. We propose that estrogen-induced genes are organized in modules: Growth of hypothalamic neurons; Amplification of the estrogen effect by progesterone; Preparative behaviors; Permissive actions on sex behavior circuitry; and Synchronization of mating behavior with ovulation. These modules may represent mechanistic routes for CNS management of successful reproduction. Moreover, new microarray results add estrogen-dependent genes, including some expressed in glia, suggesting possible hormone-dependent neuronal/ glial coordination. Molecular Psychiatry (2004) 9, 550-556. doi:10.1038/sj.mp.4001493Keywords: sex; estrogen; gene; hypothalamus; lordosis; arousal; noradrenalin; acetylcholine; oxytocin; enkephalin; opioid; GnRH; LHRH; neurotrophic; anxiety Sexual behaviors are important for psychiatry. Not only hypersexual disorders but also concerns about lack of sexual desire are prominent, internationally, in the psychiatric landscape. Further, in some traditions of psychiatric theory, sexual problems are held to be at the root of apparently unrelated syndromes. Finally, biological thought has held that sexual affiliations provide the bauplan, the structural precedent, for a wide variety of other social relations, both normal or abnormal. Fortunately, the molecular analysis of stereotyped sexual behaviors has benefited greatly from several strategic advantages: Even in mammals, simple stimuli and responses permit neural net analysis. Steroid hormones acting through nuclear receptors which are transcription factors invoke regulated gene expression, for example, in hypothalamic neurons.1 In turn, these neurons control mating behavior circuits.Drawing hormone-regulated gene expression into the explanation of mammalian sex behavior has proceeded rapidly. Here we theoretically propose a gene network-really, a micronet-downstream of estrogen action in the forebrain responsible for courtship and lordosis behavior in females. Not a massive review of the literature or an original data report, this paper comprises an attempt to draw different transcriptional systems into a new theoretical formulation. These efforts to explain hormone-driven behaviors have benefited from Rosenfeld's example of genetic network control over pituitary gland development.2 Both direct and indirect causal routes are depicted below.Causal routes, downstream from genomic action; a modular system emergent The primary sex behavior of female quadrupeds, lordosis, depends on defined physical signals: cutaneous stimuli and estrogens þ progestins 1 (E þ P). The neural circuit has been worked out; estrogen-dependent transcription in ventromedial hypothalamic cells allows permissive signals to the midbrain central gray, thus enabling the rest of the circuit. In the absence of fear or anxiety-pro...

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Effects of intrahypothalamic administration of antisense DNA for progesterone receptor mRNA on reproductive behavior and progesterone receptor immunoreactivity in female rat

Cited by 170 publications

References 35 publications

Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities.

Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities.

Estradiol-Induced Conditioned Place Preference may Require Actions at Estrogen Receptors in the Nucleus Accumbens

Hormonal symphony: steroid orchestration of gene modules for sociosexual behaviors

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