Identification of salsolinol in the mediobasal hypothalamus of lactating ewes and its relation to suckling-induced prolactin and GH release (original) (raw)
Related papers
Brain Research, 2010
The prolactin release caused by salsolinol (a derivative of dopamine, DA) in rats could be prevented by its structural analogue 1-methyl-3,4-dihydroisoqinoline (1-MeDIQ). To study the participation of salsolinol in the neural stimulatory mechanism of prolactin release in lactating sheep, we tested whether 1-MeDIQ, acting at the central nervous system (CNS) level, would diminish basal prolactin release and reduce prolactin surge induced by suckling. A series of intracerebroventricular (icv) infusions of 1-MeDIQ (5 × 60 μg/ 60 μl/30 min, at 30-min intervals) were performed in nursing ewes (n = 8) during the fifth week of lactation. Additionally, by combining these infusions with push-pull perfusion, we studied the concentration of dopaminergic components, i.e., salsolinol, DA and 3,4dihydroxyphenylacetic acid (DOPAC) within the infundibular nucleus/median eminence (IN/ME) in four of the ewes. Treatment with 1-MeDIQ significantly (P < 0.001) reduced either the basal prolactin release during the non-suckling period or the suckling-induced prolactin surge. Specifically, the suppressive effect occurred gradually, affecting both the duration and amplitude of the prolactin surge. In the control ewes, the perfusate salsolinol concentration increased significantly (P < 0.001) during suckling, while in the ewes treated with 1-MeDIQ only vestigial amounts of this compound were found during the nonsuckling period. No DA was detected in the perfusates collected from the IN/ME of control and 1-MeDIQ-treated groups and no significant differences were found in the DOPAC concentrations between these groups. In conclusion, 1-MeDIQ is able to inhibit prolactin Keywords: Salsolinol 1-MeDIQ Prolactin release Dopaminergic system lactation Nursing sheep B R A I N R E S E A R C H 1 3 0 7 ( 2 0 1 0 ) 7 2 -7 7 ⁎ Corresponding author. Fax: +48 22 7742038. E-mail address: t.misztal@ifzz.pan.pl (T. Misztal). Abbreviations: 1-MeDIQ, 1-methyl-3,4-dihydroisoqinoline; IIIv, the third brain ventricle; AP, anterior pituitary; CNS, central nervous system; DA, dopamine; DOPAC, 3,4-dihydroxyphenylacetic acid; icv, intracerebroventricular; IN/ME, infundibular nucleus/median eminence; RL, Ringer-Locke solution 0006-8993/$see front matter a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m w w w . e l s e v i e r . c o m / l o c a t e / b r a i n r e s secretion in lactating sheep, acting at the CNS level. In addition, one of the way of 1-MeDIQ action may be directed to the local salsolinol release within the mediobasal hypothalamus.
Domestic Animal Endocrinology, 2008
The aims of the present study were to determine whether salsolinol (SAL), a dopamine-related compound, is present in the bovine posterior pituitary (PP) gland, and to clarify the effect of SAL on the secretion of prolactin (PRL) in ruminants. SAL was detected in extract of bovine PP gland using high-pressure liquid chromatography with electrochemical detection (HPLC-EC). A single intravenous (i.v.) injection of SAL (5 and 10 mg/kg body weight) significantly and dose-dependently stimulated the release of PRL in goats (P < 0.05). Plasma PRL levels reached a peak 10 min after the injection, then gradually returned to basal values in 60-80 min. The PRL-releasing pattern was similar to that in response to sulpiride (a dopamine receptor antagonist). The intracerebroventricular (i.c.v.) injection of 1 mg of SAL had no significant effect on the release of PRL in calves, however, 5 mg significantly stimulated the release (P < 0.05) with peak values reached 30-40 min after the injection. Moreover, SAL significantly stimulated the release of PRL from cultured bovine anterior pituitary cells at doses of 10 −6 and 10 −5 M, compared to control cells (P < 0.05). Taken together, our data clearly show that SAL is present in extract of the PP gland of ruminants, and has PRL-releasing activity both in vivo and in vitro. Therefore, this endogenous compound is a strong candidate for the factor having PRL-releasing activity that has been previously detected in extract of the bovine PP gland.
ARTICLE IN PRESS Characteristics of prolactin-releasing response to salsolinol in vivo in cattle
The aims of the present study were to clarify the effect of salsolinol (SAL), a dopamine (DA)-derived endogenous compound, on the secretion of prolactin (PRL) in cattle. The experiments were performed from April to June using calves and cows. A single intravenous (i.v.) injection of SAL (5 mg/kg body weight [BW]) or sulpiride (a DA receptor antagonist, 0.1 mg/kg BW) significantly stimulated the release of PRL in male and female calves (P < 0.05), though the response to SAL was smaller than that to sulpiride. The secretory pattern of PRL in response to SAL or sulpiride in female calves resembled that in male calves. A single i.v. injection of SAL or sulpiride significantly stimulated the release of PRL in cows (P < 0.05). There was no significant difference in the PRL-releasing response between the SAL-and sulpiride-injected groups in cows. A single intracerebroventricular injection of SAL (10 mg/head) also significantly stimulated the release of PRL in castrated calves (P < 0.05). These results show that SAL is involved in the regulatory process for the secretion of PRL, not only in male and female calves, but also in cows. The results also suggest that the potency of the PRL-releasing response to SAL differs with the physiological status of cattle.
Journal of neuroendocrinology, 2014
In mammals, the responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis to stress is reduced during lactation and this mainly results from suckling by the offspring. The suckling stimulus causes a release of the hypothalamic 1-metyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol) (a derivative of dopamine), one of the prolactin-releasing factors. To investigate the involvement of salsolinol in the mechanism suppressing stress-induced HPA axis activity, we conducted a series of experiments on lactating sheep, in which they were treated with two kinds of isolation stress (isolation from the flock with lamb present or absent), combined with suckling and/or i.c.v infusion of salsolinol and 1-methyl-3,4-dihydro-isoqinoline (1-MeDIQ; an antagonistic analogue of salsolinol). Additionally, a push-pull perfusion of the infundibular nucleus/median eminence (IN/ME) and blood sample collection with 10-min intervals were performed during the experiments. Concentrations of perfu...
Domestic Animal Endocrinology, 2008
We have recently demonstrated that salsolinol (SAL), a dopamine (DA)-derived compound, is present in the posterior pituitary gland and is able to stimulate the release of prolactin (PRL) in ruminants. The aim of the present study was to clarify the effect that the interaction of SAL with thyrotropin-releasing hormone (TRH) or DA has on the secretion of PRL in ruminants. A single intravenous (i.v.) injection of SAL (5 mg/kg body weight (b.w.)), TRH (1 g/kg b.w.), and SAL plus TRH significantly stimulated the release of PRL in goats (P < 0.05). The cumulative response curve (area under the curve: AUC) during 120 min was 1.53 and 1.47 times greater after the injection of SAL plus TRH than either SAL or TRH alone, respectively (P < 0.05). A single i.v. injection of sulpiride (a DA receptor antagonist, 0.1 mg/kg b.w.), sulpiride plus SAL (5 mg/kg b.w.), and sulpiride plus TRH (1 g/kg b.w.) significantly stimulated the release of PRL in goats (P < 0.05). The AUC of PRL during 120 min was 2.12 and 1.78 times greater after the injection of sulpiride plus TRH than either sulpiride alone or sulpiride plus SAL, respectively (P < 0.05). In cultured bovine anterior pituitary (AP) cells, SAL (10 −6 M), TRH (10 −8 M), and SAL plus TRH significantly increased the release of PRL (P < 0.05), but the additive effect of SAL and TRH detected in vivo was not observed in vitro. In contrast, DA (10 −6 M) inhibited the TRH-, as well as SAL-induced PRL release in vitro. All together, these results clearly show that SAL can stimulate the release of PRL in ruminants. Furthermore, they also demonstrate that the additive effect of SAL and TRH on the release of PRL detected in vivo may not be mediated at the level of the AP, but that DA can overcome their releasing activity both in vivo and in vitro, confirming the dominant role of DA in the inhibitory regulation of PRL secretion in ruminants.
Involvement of salsolinol in the suckling-induced oxytocin surge in sheep
Domestic Animal Endocrinology, 2017
During lactation, the main surge of oxytocin is induced by a suckling stimulus. Previous studies have shown that salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline), a dopamine-derived compound, stimulates both the synthesis and the release of oxytocin in lactating sheep. The objective of the present study was to verify the hypothesis that salsolinol is involved in the mechanism that generates the oxytocin surge that occurs during suckling. Thus, a structural analogue of salsolinol, 1-methyl-3,4-dihydroisoquinoline (1MeDIQ), known to antagonize some of its actions, was infused into the third ventricle of the brain of lactating sheep nursing their offspring. Serial 30-min infusion of 1MeDIQ (4 Â 60 mg/60 mL) or vehicle were administered at 30-min interval from 10 AM to 2 PM. The experimental period in every ewe consisted of a nonsuckling period (10 AM-12 PM) and a suckling period (12 PM-2 PM). Blood samples were collected every 10 min, to measure plasma oxytocin concentration by RIA. In control sheep, oxytocin surges of high amplitude were observed during the suckling period. The oxytocin surges induced by suckling were significantly (P < 0.01) diminished in sheep receiving 1MeDIQ infusions as compared to those that received control infusions. However, no significant effect of 1MeDIQ was observed on basal oxytocin release, before suckling. Furthermore, oxytocin release, as measured by the area under the hormone response curve (AUC), was significantly decreased by the administration of 1MeDIQ during the suckling period. This study shows that elimination of the effect of salsolinol within the central nervous system of lactating sheep attenuates the oxytocin surge induced by suckling. Therefore, salsolinol may be an important factor in the oxytocin-stimulating pathway in lactating mammals.
2011
Salsolinol with its derivatives has been considered as a potential neurotoxin for the dopaminergic system in the human and rat brain. Investigating a sheep model for studies on the action of salsolinol within the central nervous system we examined whether this compound is able to affect the hypothalamic neuroendocrine dopaminergic (NEDA) system during its high seasonal activity, when sheep entered to anestrus under the long day conditions. Therefore, salsolinol was infused into the third ventricle of the brain in combination with the in vivo push-pull perfusion of the mediobasal hypothalamus/median eminence (MBH/ME). The effects of this drug on either perfusate noradrenaline (NA) or plasma prolactin concentration were also studied. The infusion of salsolinol resulted in rapid and permanent diminution in dopamine (DA) release into the extracellular spaces of the MBH/ME up to an undetectable level and in the 57% decrease in DA metabolite 3,4-dihydroxyphenylacetic acid concentration, c...
Animal Reproduction Science, 2019
In the present study, there was testing of the hypothesis that a centrally administered dopamine (DA) derivative, salsolinol, could affect pulsatile luteinizing hormone (LH) secretion in seasonally anestrous sheep by affecting the neuronal components of the estradiol (E2) negative feedback. In two experiments performed during early spring (increasing day length-March/April), salsolinol or Ringer-Locke solution (control) were administered into the third brain ventricle (IIIv): 1) in several injections for three consecutive days; and 2) in several hour-long infusions. In addition to determining the LH concentration (in both experiments), the abundances of gonadotropin-releasing hormone (GnRH) and kisspeptin mRNA were examined in the hypothalamus and LHβ subunit mRNA in the pituitary (Experiment 1). In Experiment 2, concentrations of DA and 3,4dihydroxyphenylacetic acid (DOPAC) were determined in perfusates collected from the infundibular nucleus/median eminence (IN/ME) by the push-pull method. In both experiments, salsolinol increased both LH pulse frequency (P < 0.05) and plasma LH concentration (P < 0.001) compared to controls. The injected salsolinol also increased (P < 0.05) the abundance of GnRH mRNA in the mediobasal hypothalamus and kisspeptin mRNA in the arcuate nucleus. The two doses of infused salsolinol decreased DA to undetectable concentrations and DOPAC concentration by 60% in perfusates collected from the IN/ME. In conclusion, exogenous salsolinol functioning centrally stimulates pulsatile LH secretion in sheep during seasonal anestrus. It is suggested that salsolinol may have this effect by reducing the activity of the hypothalamic neuroendocrine dopaminergic system, which results in an increase in both kisspeptin and GnRH neurons activity.
Effect of salsolinol on ACTH and cortisol response to handling stress in early anestrous sheep
Czech Journal of Animal Science, 2017
Inhibition of hypothalamic–pituitary–adrenal (HPA) axis activity by salsolinol was demonstrated in lactating sheep. We assessed whether salsolinol regulates, besides lactation, also adrenocorticotropic hormone (ACTH) and cortisol release, and if its action is prolactin-dependent. We examined two groups of early anestrous sheep, which received for three days salsolinol or vehicle-only intracerebroventricular injections, and a group of lactating sheep injected with the vehicle only. On day 3, blood samples were collected for over six hours and the anterior pituitary was dissected. Plasma ACTH, cortisol, and prolactin concentrations, and proopiomelanocortin (POMC) and prolactin (PRL) mRNA expression within the anterior pituitary were assayed. In all groups, ACTH and cortisol concentrations were higher (P < 0.05 and P < 0.001) during the first half of sampling than in the second half; there were no differences in prolactin concentration. Lactating sheep had lower (P < 0.05 and ...