Hormone secretion often occurs in a pulsatile manner. In this review, we discuss two rhythms of i... more Hormone secretion often occurs in a pulsatile manner. In this review, we discuss two rhythms of in vivo prolactin release in female rats and the ongoing research that we and others have performed aiming to understand the mechanisms underlying them. The peptide hormone oxytocin appears to play an important role in both rhythms. One rhythm occurs during the first half of pregnancy, but can also be induced in ovariectomised rats. This is characterised by a circadian pattern with two prolactin surges per day. Two methods for triggering this rhythm are discussed, each utilising a unique physiological pathway that includes oxytocin action, presumably on pituitary lactotrophs. The second rhythm occurs during the oestrous cycle and is characterised by a surge of prolactin on the afternoon of pro-oestrus. We discuss recent findings that oxytocin is more effective at stimulating prolactin release from lactotrophs taken from animals on the afternoon of pro-oestrus than from those of animals on the morning of dioestrus 1, raising the possibility that this hormone plays a physiological role in the regulation of prolactin secretion during the oestrous cycle.
A secondary surge of prolactin has been recently characterised on the afternoon of oestrus. Becau... more A secondary surge of prolactin has been recently characterised on the afternoon of oestrus. Because the noradrenergic nucleus locus coeruleus participates in the genesis of the pro-oestrous and steroid-induced surges of prolactin, the aim of the present study was to investigate the importance of locus coeruleus norepinephrine in the generation of the prolactin surge of oestrus. For this purpose, we initially re-evaluated the profile of prolactin secretion during the oestrous cycle to verify whether this surge of prolactin was physiological and specific to the day of oestrus. Thereafter, the following were evaluated: (i) the effect of locus coeruleus lesion on the secondary surge of prolactin and on norepinephrine concentration in the medial preoptic area (MPOA), medial basal hypothalamus (MBH) and paraventricular nucleus (PVN) during the day of oestrus and (ii) locus coeruleus neurones activity during the same day by Fos immunoreactivity. Locus coeruleus lesion completely blocked the prolactin surge of oestrus in all rats studied and also significantly reduced norepinephrine concentration in the MPOA, MBH and PVN during the day of oestrus. The number of double-labelled tyrosine hydroxylase/Fos immunoreactive neurones in locus coeruleus was significantly higher at 14.00Â h of oestrus, suggesting an increase in its activity preceding the prolactin surge that generally occurs at 15.00Â h. Therefore, the increase in locus coeruleus activity on the afternoon of oestrus supports the data obtained with bilateral lesion of this nucleus, suggesting a stimulatory role of locus coeruleus norepinephrine in the genesis of the secondary surge of prolactin.
Noradrenaline has been shown to modulate the ovarian-steroid feedback on luteinising-hormone (LH)... more Noradrenaline has been shown to modulate the ovarian-steroid feedback on luteinising-hormone (LH) release. However, despite the high amount of evidence accumulated over many years, the role of noradrenaline in LH regulation is still not clearly understood. The present study aimed to further investigate the involvement of noradrenaline in the negative-feedback effect of oestradiol and progesterone on basal LH secretion. In experiment 1, ovariectomised (OVX) rats received a single injection of oil, oestradiol, or progesterone at 09.00–10.00 h and were decapitated 30 or 60 min later. Levels of noradrenaline and its metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), were determined in microdissections of the preoptic area (POA) and medial basal hypothalamus-median eminence (MBH-ME) and correlated with LH secretion. Basal LH levels were decreased 30 and 60 min after oestradiol or progesterone injection, and this hormonal response was significantly correlated with a reduction in POA MHPG levels, which reflect noradrenaline release. In addition, noradrenaline levels in the POA were increased, whereas noradrenaline turnover (MHPG/noradrenaline ratio) was decreased 60 min after the injection of both hormones. No effect was found in the MBH-ME. In experiment 2, i.c.v. administration of noradrenaline (60 nmol), performed 15 min before oestradiol or progesterone injection in jugular vein-cannulated OVX rats, completely prevented the ovarian steroid-induced inhibition of LH secretion. The data obtained provide direct evidence that LH secretion in OVX rats is positively regulated by basal noradrenergic activity in the POA, and its reduction appears to play a role in the negative-feedback effect of ovarian steroids on LH secretion in vivo.
Locus coeruleus (LC) is involved in the LHRH regulation by gonadal steroids. We investigated the ... more Locus coeruleus (LC) is involved in the LHRH regulation by gonadal steroids. We investigated the expression of progesterone and estrogen receptors (PR; ER) in LC neurons of ERα (αERKO) or ERβ (βERKO) knockout mice, and their wild-type (αWT and βWT). Immunocytochemical studies showed that LC expresses PR and both ERs, although ERβ was more abundant. Estradiol benzoate (EB) decreased ERα-positive cells in WT and βERKO mice, and progesterone caused a further reduction, whereas none of the steroids influenced ERβ expression. ERβ deletion increased ERα while ERα deletion did not alter ERβ expression. In both WT mice, EB increased PR expression, which was diminished by progesterone. These steroid effects were also observed in αERKO animals but to a lesser extent, suggesting that ERα is partially responsible for the estrogenic induction of PR in LC. Steroid effects on PR in βERKO mice were similar to those in the αERKO but to a lesser extent, probably because PR expression was already high in the oil-treated group. This expression seems to be specific of LC neurons, since it was not observed in other areas studied, the preoptic area and ventromedial nucleus of hypothalamus. These findings show that LC in mice expresses αER, βER, and PR, and that a balance between them may be critical for the physiological control of reproductive function.
The activity of the hypothalamic-pituitary-adrenal axis is modulated by the norepinephrinergic sy... more The activity of the hypothalamic-pituitary-adrenal axis is modulated by the norepinephrinergic system and, in females, also by the ovarian hormones. We investigated the role of ovarian steroids and the locus coeruleus (LC) on stress-induced corticosterone secretion in female rats. Ovariectomized rats without hormonal replacement (OVX) or treated with estradiol (OVE) or estradiol plus progesterone (OVEP) were subjected to jugular cannulation. Immediately after that, each hormonal treatment group was subjected to LC lesion or sham surgery or no brain surgery. After 24Â h, blood samples of all 9 groups were collected before and after ether inhalation. Other four groups (OVX control, sham and lesioned, and OVE) were perfused for glucocorticoid receptor (GR) immunocytochemistry in hippocampal CA1 neurons and paraventricular nucleus (PVN). Estradiol replacement decreased while LC lesions increased stress-induced corticosterone secretion. The effect of LC lesion was potentiated with the removal of ovarian steroids. Since GR expression of lesioned animals decreased in the hippocampus, but not in PVN, we suggest that the effect of LC lesion on corticosterone secretion could be due to a reduction in the efficiency of the negative feedback system in the CA1 neurons. However, this mechanism is not involved in the estradiol modulation on corticosteroid secretion, as no change in GR expression was observed in estradiol-treated animals.
Hormone secretion often occurs in a pulsatile manner. In this review, we discuss two rhythms of i... more Hormone secretion often occurs in a pulsatile manner. In this review, we discuss two rhythms of in vivo prolactin release in female rats and the ongoing research that we and others have performed aiming to understand the mechanisms underlying them. The peptide hormone oxytocin appears to play an important role in both rhythms. One rhythm occurs during the first half of pregnancy, but can also be induced in ovariectomised rats. This is characterised by a circadian pattern with two prolactin surges per day. Two methods for triggering this rhythm are discussed, each utilising a unique physiological pathway that includes oxytocin action, presumably on pituitary lactotrophs. The second rhythm occurs during the oestrous cycle and is characterised by a surge of prolactin on the afternoon of pro-oestrus. We discuss recent findings that oxytocin is more effective at stimulating prolactin release from lactotrophs taken from animals on the afternoon of pro-oestrus than from those of animals on the morning of dioestrus 1, raising the possibility that this hormone plays a physiological role in the regulation of prolactin secretion during the oestrous cycle.
A secondary surge of prolactin has been recently characterised on the afternoon of oestrus. Becau... more A secondary surge of prolactin has been recently characterised on the afternoon of oestrus. Because the noradrenergic nucleus locus coeruleus participates in the genesis of the pro-oestrous and steroid-induced surges of prolactin, the aim of the present study was to investigate the importance of locus coeruleus norepinephrine in the generation of the prolactin surge of oestrus. For this purpose, we initially re-evaluated the profile of prolactin secretion during the oestrous cycle to verify whether this surge of prolactin was physiological and specific to the day of oestrus. Thereafter, the following were evaluated: (i) the effect of locus coeruleus lesion on the secondary surge of prolactin and on norepinephrine concentration in the medial preoptic area (MPOA), medial basal hypothalamus (MBH) and paraventricular nucleus (PVN) during the day of oestrus and (ii) locus coeruleus neurones activity during the same day by Fos immunoreactivity. Locus coeruleus lesion completely blocked the prolactin surge of oestrus in all rats studied and also significantly reduced norepinephrine concentration in the MPOA, MBH and PVN during the day of oestrus. The number of double-labelled tyrosine hydroxylase/Fos immunoreactive neurones in locus coeruleus was significantly higher at 14.00Â h of oestrus, suggesting an increase in its activity preceding the prolactin surge that generally occurs at 15.00Â h. Therefore, the increase in locus coeruleus activity on the afternoon of oestrus supports the data obtained with bilateral lesion of this nucleus, suggesting a stimulatory role of locus coeruleus norepinephrine in the genesis of the secondary surge of prolactin.
Noradrenaline has been shown to modulate the ovarian-steroid feedback on luteinising-hormone (LH)... more Noradrenaline has been shown to modulate the ovarian-steroid feedback on luteinising-hormone (LH) release. However, despite the high amount of evidence accumulated over many years, the role of noradrenaline in LH regulation is still not clearly understood. The present study aimed to further investigate the involvement of noradrenaline in the negative-feedback effect of oestradiol and progesterone on basal LH secretion. In experiment 1, ovariectomised (OVX) rats received a single injection of oil, oestradiol, or progesterone at 09.00–10.00 h and were decapitated 30 or 60 min later. Levels of noradrenaline and its metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), were determined in microdissections of the preoptic area (POA) and medial basal hypothalamus-median eminence (MBH-ME) and correlated with LH secretion. Basal LH levels were decreased 30 and 60 min after oestradiol or progesterone injection, and this hormonal response was significantly correlated with a reduction in POA MHPG levels, which reflect noradrenaline release. In addition, noradrenaline levels in the POA were increased, whereas noradrenaline turnover (MHPG/noradrenaline ratio) was decreased 60 min after the injection of both hormones. No effect was found in the MBH-ME. In experiment 2, i.c.v. administration of noradrenaline (60 nmol), performed 15 min before oestradiol or progesterone injection in jugular vein-cannulated OVX rats, completely prevented the ovarian steroid-induced inhibition of LH secretion. The data obtained provide direct evidence that LH secretion in OVX rats is positively regulated by basal noradrenergic activity in the POA, and its reduction appears to play a role in the negative-feedback effect of ovarian steroids on LH secretion in vivo.
Locus coeruleus (LC) is involved in the LHRH regulation by gonadal steroids. We investigated the ... more Locus coeruleus (LC) is involved in the LHRH regulation by gonadal steroids. We investigated the expression of progesterone and estrogen receptors (PR; ER) in LC neurons of ERα (αERKO) or ERβ (βERKO) knockout mice, and their wild-type (αWT and βWT). Immunocytochemical studies showed that LC expresses PR and both ERs, although ERβ was more abundant. Estradiol benzoate (EB) decreased ERα-positive cells in WT and βERKO mice, and progesterone caused a further reduction, whereas none of the steroids influenced ERβ expression. ERβ deletion increased ERα while ERα deletion did not alter ERβ expression. In both WT mice, EB increased PR expression, which was diminished by progesterone. These steroid effects were also observed in αERKO animals but to a lesser extent, suggesting that ERα is partially responsible for the estrogenic induction of PR in LC. Steroid effects on PR in βERKO mice were similar to those in the αERKO but to a lesser extent, probably because PR expression was already high in the oil-treated group. This expression seems to be specific of LC neurons, since it was not observed in other areas studied, the preoptic area and ventromedial nucleus of hypothalamus. These findings show that LC in mice expresses αER, βER, and PR, and that a balance between them may be critical for the physiological control of reproductive function.
The activity of the hypothalamic-pituitary-adrenal axis is modulated by the norepinephrinergic sy... more The activity of the hypothalamic-pituitary-adrenal axis is modulated by the norepinephrinergic system and, in females, also by the ovarian hormones. We investigated the role of ovarian steroids and the locus coeruleus (LC) on stress-induced corticosterone secretion in female rats. Ovariectomized rats without hormonal replacement (OVX) or treated with estradiol (OVE) or estradiol plus progesterone (OVEP) were subjected to jugular cannulation. Immediately after that, each hormonal treatment group was subjected to LC lesion or sham surgery or no brain surgery. After 24Â h, blood samples of all 9 groups were collected before and after ether inhalation. Other four groups (OVX control, sham and lesioned, and OVE) were perfused for glucocorticoid receptor (GR) immunocytochemistry in hippocampal CA1 neurons and paraventricular nucleus (PVN). Estradiol replacement decreased while LC lesions increased stress-induced corticosterone secretion. The effect of LC lesion was potentiated with the removal of ovarian steroids. Since GR expression of lesioned animals decreased in the hippocampus, but not in PVN, we suggest that the effect of LC lesion on corticosterone secretion could be due to a reduction in the efficiency of the negative feedback system in the CA1 neurons. However, this mechanism is not involved in the estradiol modulation on corticosteroid secretion, as no change in GR expression was observed in estradiol-treated animals.
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