Marcos García-Juárez

Benemérita Universidad Autónoma de Puebla, Puebla, Estado de Baja California, Mexico

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Publications (10)28.94 Total impact

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    Article: The nitric oxide pathway participates in lordosis behavior induced by central administration of leptin.
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    ABSTRACT: Intracerebroventricular (icv) administration of leptin facilitates lordosis behavior in ad libitum-fed, estrogen-primed rats. The cellular mechanism involved in this response is unknown. The present study tested the hypothesis that the nitric oxide-guanylyl cyclase, cGMP-dependent protein kinase (PKG) pathway is involved in the facilitation of lordosis behavior induced by the central administration of leptin. We tested the importance of the nitric oxide/cGMP pathway for lordosis stimulation by either icv infusion of a nitric oxide synthase inhibitor (L-NAME) or a nitric oxide-dependent, soluble guanylyl cyclase inhibitor (ODQ) 30 min before leptin administration (1 μg). This dose of leptin reliably induced lordosis behavior in ovariectomized estradiol benzoate treated rats. The lordosis induced by leptin at 1 and 2h after infusion was significantly reduced by the previous injection of either L-NAME or by ODQ. Intracerebroventricular infusion of the PKG inhibitor (KT5823) 30 min before leptin infusion, also significantly inhibited the lordosis behavior induced by leptin at 1 and 2h after hormone administration. These data support the hypothesis that the nitric oxide/cGMP/PKG pathway is involved in the facilitation of lordosis by leptin in estrogen-primed female rats.
    Neuropeptides 02/2012; 46(1):49-53. · 1.55 Impact Factor
  • Article: Progesterone receptor isoforms differentially regulate the expression of tryptophan and tyrosine hydroxylase and glutamic acid decarboxylase in the rat hypothalamus.
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    ABSTRACT: Progesterone exerts a variety of actions in the brain through the interaction with its receptors (PR) which have two isoforms with different function and regulation: PR-A and PR-B. Progesterone may modulate neurotransmission by regulating the expression of neurotransmitters synthesizing enzymes or their receptors in several brain regions. The role of PR isoforms in this modulation is unknown. We explored the role of PR isoforms in the regulation of tryptophan (TPH) and tyrosine (TH) hydroxylase, and glutamic acid decarboxylase (GAD) expression in the hypothalamus of ovariectomized rats. Two weeks after ovariectomy, animals were subcutaneously injected with 5 μg of estradiol benzoate (EB), and 40 h later, progesterone (P) was intracerebroventricularly (ICV) injected. Each animal received two ICV injections of 1 μg/μl (4 nmol) of PR-B and total PR (PR-A+PR-B) sense or antisense (As) oligonucleotides (ODNs). First injection was made immediately before sc EB injection, and 24h later animals received the second one. Twenty-four hours after P administration, rats were euthanized and brains removed to measure the expression of PR-A and PR-B, TPH, TH and GAD by Western blot. We observed that sense ODNs modified neither PR isoforms nor enzymes expression in the hypothalamus, whereas PR A+B antisense (PR A+B As) clearly decreased the expression of both PR isoforms in this region. ICV administration of PR-B As only decreased PR-B isoform expression with no significant effects on PR-A expression. A differential protein expression of TPH, TH and GAD was observed after PR isoforms antisense administration. PR-B As administration decreased the expression of TPH (65% with respect to control). In contrast, PR A+B As and PR-B As administration increased (51.6% and 34.4%, respectively) TH expression. The administration of PR A+B As and PR-B As diminished GAD expression (33.4% and 41.6%, respectively). Our findings indicate that PR isoforms play a differential role in the regulation of the content of TPH, TH and GAD in the rat hypothalamus.
    Neurochemistry International 06/2011; 59(5):671-6. · 2.86 Impact Factor
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    Article: Differential effects of progesterone and genital stimulation on sequential inhibition of estrous behavior and progesterone receptor expression in the rat brain.
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    ABSTRACT: The effect of genital stimulation, either by vaginocervical stimulation (VCS) using a calibrated vaginal probe combined with manual flank stimulation (FS), or by mounts performed by the male, on the hypothalamus and preoptic area concentration of the progesterone receptors A (PR-A) and B (PR-B) was assessed in ovariectomized (ovx) estrogen-primed rats. VCS/FS or stimulation provided by male mounts, even without intromission, significantly decreased PR-B concentration in the hypoythalamus. Down regulation of PR produced by genital stimulation was quantitatively similar to that elicited by progesterone (P) administration. Bilateral or unilateral transection of the pelvic or the pudendal nerves prevented down regulation elicited by VCS/FS. Repeated VCS/FS elicited lordosis behavior in most ovx estrogen primed rats, but the lordosis intensity was lower than that observed in response to P. P administered to ovx estrogen primed rats, induced sequential inhibition, i.e., failure to display estrous behavior in response to a second P injection (24h after the initial P injection). VCS/FS failed to elicit sequential inhibition, since rats responded with normal estrous behavior to the second injection of P. This suggests that down regulation by VCS, by contrast with P, failed to inhibit the subpopulation of PR involved in the facilitation of estrous behavior by P.
    Brain research bulletin 05/2011; 85(3-4):201-6. · 2.18 Impact Factor
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    Article: Leptin facilitates lordosis behavior through GnRH-1 and progestin receptors in estrogen-primed rats.
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    ABSTRACT: Dose response curves for leptin facilitation of estrous behavior (lordosis and proceptivity) were made by infusing the peptide into the lateral ventricle (icv) of ovariectomized (ovx), ad libitum-fed rats injected 40h previously with 5μg of estradiol benzoate. Leptin doses of 1 and 3μg produced significant lordosis quotient at 60min post-injection, with maximal lordosis being displayed at 120min. Yet the intensity of lordosis was weak, and a high incidence of rejection behaviors was found. Moreover, leptin did not induce significant proceptive behaviors at any dose. The leptin doses of 1 and 3μg were selected for determining whether antide, a GnRH-1 receptor antagonist, or the progestin receptor antagonist RU486 could modify the lordosis response to leptin. Icv injection of either antide or RU486 1h before leptin significantly depressed leptin facilitation of lordosis. The results suggest that leptin stimulates lordosis by releasing GnRH, which in turn activates GnRH-1 and progestin receptors. The physiological role of leptin in the control of estrous behavior remains to be determined.
    Neuropeptides 02/2011; 45(1):63-7. · 1.55 Impact Factor
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    Article: A role for Src kinase in progestin facilitation of estrous behavior in estradiol-primed female rats.
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    ABSTRACT: This study tested the hypothesis that the Src/Raf/MAPK signaling pathway is involved in the facilitation of the lordosis and proceptive behaviors induced by progesterone (P) and its ring A-reduced metabolites in ovariectomized, estradiol-primed rats. Intraventricular (icv) infusion of PP2 (7.5, 15 and 30 microg), a Src kinase inhibitor, significantly depressed P-dependent estrous behavior (lordosis and proceptivity) in estradiol-primed rats. Icv infusion of 30 microg of PP2 also significantly attenuated estrous behavior induced by the ring A-reduced P metabolites 5 alpha-dihydroprogesterone (5 alpha-DHP) and 5 alpha-pregnan-3alpha-ol-20-one (allopregnanolone). PP2 did not inhibit estrous behavior induced by administration of high doses of estradiol alone to ovariectomized rats. We also assessed if the ventromedial hypothalamus (VMH) is one of the neural sites at which progestins activate Src signaling to facilitate estrous behavior. Bilateral administration of 15 microg of PP2 into the VMH inhibited the stimulation of both lordosis and proceptive behaviors elicited by subcutaneous P administration to estradiol-primed rats. These results suggest that progestins act through Src/Raf/MAPK signaling to initiate estrous behaviors in estrogen-primed rats. This event is one component of the cellular pathways leading to the display of estrous behaviors induced by P and its ring A-reduced metabolites in female rats.
    Hormones and Behavior 03/2010; 58(2):223-9. · 3.87 Impact Factor
  • Article: Role of progesterone receptor isoforms in female sexual behavior induced by progestins in rats.
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    ABSTRACT: 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: 5alpha-pregnan-3,20-dione (5alpha-DHP), and 5beta,3beta-pregnan-20-one (5beta,3beta-Pgl) in adult ovariectomized rats. Two weeks after ovariectomy, the animals were injected subcutaneously with 5 microg 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 5alpha-DHP although with less efficacy than total PR antisense oligonucleotides, but the former inhibited lordosis induced by 5beta,3beta-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.
    Neuroendocrinology 07/2009; 90(1):73-81. · 2.38 Impact Factor
  • Article: Lordosis facilitation by LHRH, PGE2 or db-cAMP requires activation of the kinase A signaling pathway in estrogen primed rats.
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    ABSTRACT: Dose-response curves for lordosis and proceptive behaviors were obtained for luteinizing hormone releasing hormone (LHRH), prostaglandin E2 (PGE2) and dibutyryl cyclic AMP (db-cAMP), by infusing them in the right lateral ventricle (i.c.v.) of ovariectomized (OVX) estradiol benzoate (E2B; 2 microg) treated rats. Two dose levels, one producing the maximal effect and the other one producing a submaximal response (approximately ED50) were selected for testing the capacity of Rp-cAMPS, a kinase A blocker, to modify the behavioral response to the three compounds. I.c.v. injections of Rp-cAMPS, significantly depressed both lordosis and proceptive responses induced by LHRH, PGE2 and db-cAMP. The results show that these agents use the cAMP-kinase A signaling pathway to elicit their stimulating effect on estrous behavior in the rat.
    Pharmacology Biochemistry and Behavior 02/2007; 86(1):169-75. · 2.53 Impact Factor
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    Article: Differential effect of kinase A and C blockers on lordosis facilitation by progesterone and its metabolites in ovariectomized estrogen-primed rats.
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    ABSTRACT: Dose response curves for lordosis behavior was obtained for progesterone (P) and its two ring A-reduced metabolites: 5alpha-pregnanedione (alpha-DHP) and 5alpha,3alpha-pregnanolone (5alpha,3alpha-Pgl) by infusing these progestins in the right lateral ventricle (rlv) of ovariectomized (ovx) estradiol-treated rats (2 microg estradiol benzoate; EB), 40 h before intracerebro-ventricular (icv) injection. Effective doses 50 (ED50) revealed that ring A-reduced progestins were more potent than P itself to induce lordosis behavior. Two dose levels, one producing the maximal effect and the other one producing a submaximal response (ED50-ED60), were selected for testing the capacity of RpAMPS, a kinase A blocker, and H7, a kinase C blocker, to modify the response to the three progestins. rlv injection of RpAMPS significantly depressed the lordosis response to the two dose levels of P and alpha-DHP but failed to significantly inhibit that of 5alpha,3alpha-Pgl. The administration of H7 prevented the effect of both 5alpha-reduced progestins without affecting the response to P. The results suggest that P and its ring A-reduced metabolites stimulate lordosis behavior through different cellular mechanisms: P acting mainly through the cAMP-kinase system; alpha-DHP through both kinase A and kinase C signaling pathways and 5alpha,3alpha-Pgl through the kinase C system.
    Hormones and Behavior 04/2006; 49(3):398-404. · 3.87 Impact Factor
  • Article: Estradiol and testosterone modulate the anesthetic action of the GABA-A agonist THIP, but not of the neurosteroid 3alpha,5beta-pregnanolone in the rat.
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    ABSTRACT: As sex steroids modify the number and distribution of brain gamma-aminobutyric acid (GABA)A receptor subunits, we investigated the potential modulation of anesthesia, induced by agents acting on the GABAA receptor, by estrogen and androgen. To assess possible effects of sex and hormonal condition (i.e., intact vs castrate; estradiol vs testosterone treatment) on the anesthetic effect of a GABAA agonist, THIP (4,5,6,7-tetrahydroisoxazolo[5,4,-c]pyridin-3-ol hydrochloride), and an allosteric modulator of the GABAA receptor: 3alpha-hydroxy-5beta-pregnan-20-one (epipregnanolone). The potencies of THIP and epipregnanolone for inducing loss of the righting response were compared between: (a) female and male rats; (b) intact and castrated animals of each sex; (c) untreated castrates and castrates given estradiol or testosterone. Sex and endocrine condition influenced sensitivity to i.v. THIP for the induction of anesthesia. ED50 values were: gonadectomized females, 80 mg/kg>intact males, 50 mg/kg>proestrous females, 35 mg/kg>gonadectomized males, 28 mg/kg. Estradiol benzoate (EB; 3 microg/day for 5 days) significantly increased THIP sensitivity in gonadectomized females: THIP+EB: ED50=26 mg/kg vs THIP+sesame oil: ED50=94 mg/kg, while testosterone propionate (TP; 10 mg injected 24 h before THIP) decreased THIP sensitivity in orchidectomized males when compared with vehicle-injected animals (ED50=72 mg/kg vs 22 mg/kg, respectively). Results suggest that estrogen increases the density or availability of GABAA receptor subtypes on which THIP acts, while testosterone exerts the opposite effect. Neither sex nor gonadal condition influenced the anesthetic action of epipregnanolone as a similar potency was found in intact and in gonadectomized males and females.
    Psychopharmacologia 03/2004; 172(3):283-90. · 4.08 Impact Factor
  • Article: Estradiol and testosterone modulate the anesthetic action of the GABA-A agonist THIP, but not of the neurosteroid 3a,5ß-pregnanolone in the rat
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    ABSTRACT: RationaleAs sex steroids modify the number and distribution of brain -aminobutyric acid (GABA)A receptor subunits, we investigated the potential modulation of anesthesia, induced by agents acting on the GABAA receptor, by estrogen and androgen.ObjectivesTo assess possible effects of sex and hormonal condition (i.e., intact vs castrate; estradiol vs testosterone treatment) on the anesthetic effect of a GABAA agonist, THIP (4,5,6,7-tetrahydroisoxazolo[5,4,-c]pyridin-3-ol hydrochloride), and an allosteric modulator of the GABAA receptor: 3-hydroxy-5-pregnan-20-one (epipregnanolone).MethodsThe potencies of THIP and epipregnanolone for inducing loss of the righting response were compared between: (a) female and male rats; (b) intact and castrated animals of each sex; (c) untreated castrates and castrates given estradiol or testosterone.ResultsSex and endocrine condition influenced sensitivity to i.v. THIP for the induction of anesthesia. ED50 values were: gonadectomized females, 80mg/kg > intact males, 50mg/kg > proestrous females, 35mg/kg > gonadectomized males, 28mg/kg. Estradiol benzoate (EB; 3g/day for 5days) significantly increased THIP sensitivity in gonadectomized females: THIP + EB: ED50=26mg/kg vs THIP + sesame oil: ED50=94mg/kg, while testosterone propionate (TP; 10mg injected 24h before THIP) decreased THIP sensitivity in orchidectomized males when compared with vehicle-injected animals (ED50=72mg/kg vs 22mg/kg, respectively).ConclusionsResults suggest that estrogen increases the density or availability of GABAA receptor subtypes on which THIP acts, while testosterone exerts the opposite effect. Neither sex nor gonadal condition influenced the anesthetic action of epipregnanolone as a similar potency was found in intact and in gonadectomized males and females.
    Psychopharmacologia 02/2004; 172(3):283-290. · 4.08 Impact Factor