Ring a reduced progestins potently stimulate estrous behavior in rats: Paradoxical effect through the progesterone receptor

Beyer, Carlos; González‐Flores, Oscar; González‐Mariscal, Gabriela

doi:10.1016/0031-9384(95)00141-5

Cited by 58 publications

(55 citation statements)

References 51 publications

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“…However, our results suggest that PR participates in the lordosis behavior induced by these progestins. This idea is supported by the fact that the intracerebral and systemic administration of the antiprogestin RU 486 blocked the estrous behavior induced by progesterone and some of its ring A reduced metabolites, and by GnRH [9, 13, 50]. Despite this, there are no data showing whether any ring-A-reduced progestin induces a differential downregulation of the PR-A or PR-B isoform.…”

Section: Discussionmentioning

confidence: 74%

“…However, another possibility is that PR acts as a common molecular effector that mediates the facilitatory actions of such progestins on lordosis. This idea is supported by the ability of the PR antagonist RU 486 to attenuate the behavioral effects of reduced progestins when they are administered systemically or intracerebrally [9,10,11,12,13]. …”

Section: Introductionmentioning

confidence: 74%

“…It is important to mention that we always used treatments with EB + progestins since it has been clearly demonstrated that in ovariectomized rats the administration of EB alone does not significantly induce estrous behavior [9, 13]. Progestin doses were selected according to previously established dose-response curves [10].…”

Section: Methodsmentioning

confidence: 99%

“…However, reduced progestins facilitate lordosis when implanted into the ventromedial hypothalamic nucleus [5, 6] and preoptic area [5, 7, 8]. Moreover, when injected intravenously and intracerebroventricularly, the ring A reduced metabolites stimulate the estrous behavior more potently than progesterone itself [9, 10]. …”

Section: Introductionmentioning

confidence: 99%

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Role of Progesterone Receptor Isoforms in Female Sexual Behavior Induced by Progestins in Rats

et al. 2009

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Progesterone and its ring A reduced metabolites regulate female sexual behavior through the direct or indirect activation of progesterone receptor (PR) which has two isoforms with different function and regulation: PR-A and PR-B. The contribution of each PR isoform to the regulation of lordosis in rats is unknown. We explored the role of PR isoforms in lordosis display induced by progesterone and two of its ring A reduced metabolites: 5α-pregnan-3,20-dione (5α-DHP), and 5β,3β-pregnan-20-one (5β,3β-Pgl) in adult ovariectomized rats. Two weeks after ovariectomy, the animals were injected subcutaneously with 5 μg of estradiol benzoate (EB), and 40 h later, progestins were injected intracerebroventricularly. PR-B and total PR (PR-A + PR-B) sense or antisense oligonucleotides were administered intracerebroventricularly immediately before EB injection and 24 h later. Lordosis was evaluated 30, 120 and 240 min after progestin administration. Western blot analysis of both PR isoforms was performed in the hypothalamus and preoptic area 24 h after lordosis tests. All progestins induced maximal lordosis 120 min after administration, and antisense oligonucleotides against both PR isoforms inhibited lordosis in all animals. PR-B antisense oligonucleotides also inhibited lordosis induced by progesterone and 5α-DHP although with less efficacy than total PR antisense oligonucleotides, but the former inhibited lordosis induced by 5β,3β-Pgl in a similar manner as total PR antisense oligonucleotides. In the hypothalamus and preoptic area, the content of both PR isoforms or PR-B alone was diminished by the administration of total or PR-B antisense oligonucleotides, respectively. These results suggest that the PR-B isoform is essential for the display of the lordosis behavior in rats.

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Section: Discussionmentioning

confidence: 74%

Section: Introductionmentioning

confidence: 74%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Role of Progesterone Receptor Isoforms in Female Sexual Behavior Induced by Progestins in Rats

et al. 2009

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“…Systemic administration of P 4 or 3α,5α-THP can facilitate sexual receptivity of rats [57, 58, 59, 60]. Systemic P 4 , which facilitates sexual receptivity of EB-primed rats, increases 3α,5α-THP levels in whole brain [50]and the midbrain VTA [19, 61], and increases firing of neurons in the midbrain VTA within 60 s [62].…”

Section: Discussionmentioning

confidence: 99%

Lordosis of Rats Is Modified by Neurosteroidogenic Effects of Membrane Benzodiazepine Receptors in the Ventral Tegmental Area

Frye¹,

Petralia²

2003

Neuroendocrinology

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Progestins modulate lordosis through actions in the ventral tegmental area (VTA). Whether neurosteroidogenesis of 5α-pregnan-3α-ol-20-one (3α,5α-THP), involving mitochondrial benzodiazepine receptors (MBR), is important for lordosis was investigated. Ovariectomized (Ovx), hormone-primed rats (experiments 1, 3, 5, 6) and rats in behavioral estrus (experiments 2 and 4) were unilaterally infused via chronic guide cannula to the VTA with a MBR agonist, N,N-dihexyl-2-(4-fluorophenyl) indole-30-acetamide (FGIN 1–27) or antagonist 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboximide (PK-11195). Experiment 1: Estradiol benzoate (EB)-primed (25 µg) rats administered 0 or 25 µg progesterone (P₄) SC showed increased lordosis when infused with 5.0 µg FGIN 1–27 to the VTA; those administered 100 or 200 µg P₄ SC exhibited greater lordosis when infused with 2.5 or 5.0 µg FGIN, relative to saline-infused rats. Experiment 2: Rats, near the termination of behavioral estrus, infused with 2.5 or 5.0 µg of FGIN 1–27 to the VTA, showed increased lordosis compared to that seen following vehicle administration. Experiment 3: EB-primed rats administered 200 or 500 µg P₄ SC showed decreased lordosis when infused with 100, 200, or 400 ng PK-11195, relative to saline-infused rats. Experiment 4: Rats infused at the peak of behavioral estrus with 100, 200, or 400 ng PK-11195 to the VTA exhibited reduced lordosis compared to that seen following vehicle administration. Experiment 5: 3α,5α-THP (100 ng) infusions to the VTA reinstated lordosis of hormone-primed rats infused with PK-11195 (100 ng) to the VTA. Experiment 6: FGIN 1–27 (5.0 µg) and PK-11195 (100 ng) infusions aimed at the VTA respectively increased and decreased midbrain levels of 3α,5α-THP compared to vehicle. Notably, the specific effects observed with infusions to the VTA were not seen with infusions to the control site, the substantia nigra. These data suggest that neurosteroidogenesis involving MBRs in the VTA mediates lordosis of hormone-primed or behavioral estrous rats.

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Indomethacin Inhibits Lordosis Induced by Ring A-Reduced Progestins: Possible Role of 3α-Oxoreduction in Progestin-Facilitated Lordosis

Beyer

González‐Flores

Ramírez-Orduña

et al. 1999

Hormones and Behavior

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Ring a reduced progestins potently stimulate estrous behavior in rats: Paradoxical effect through the progesterone receptor

Cited by 58 publications

References 51 publications

Role of Progesterone Receptor Isoforms in Female Sexual Behavior Induced by Progestins in Rats

Role of Progesterone Receptor Isoforms in Female Sexual Behavior Induced by Progestins in Rats

Lordosis of Rats Is Modified by Neurosteroidogenic Effects of Membrane Benzodiazepine Receptors in the Ventral Tegmental Area

Indomethacin Inhibits Lordosis Induced by Ring A-Reduced Progestins: Possible Role of 3α-Oxoreduction in Progestin-Facilitated Lordosis

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