Size heterogeneity of plasma prolactin in the rat: TRH and serotonin-induced changes.
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Biomedical subjects
Publications and source records attributed to R R Gala.
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Plasma prolactin (PRL) levels were investigated in chronically catheterized control, sham-lesioned, and amygdala (AMYG)-lesioned rats under a variety of conditions. Ovariectomized (OVX) rats injected with 0.5 mg of polyestradiol phosphate (PEP) exhibited a circadian rhythm of PRL secretion characteristic of proestrus rats. Small bilateral lesions of the central AMYG area had no effect on this pattern of PRL secretion in animals bled over a 24-h period, 1 week following lesioning. A second group of rats bearing lesions or sham lesions of the corticomedial AMYG nuclei were studied at 1, 2 and 3 weeks following surgery and PEP treatment. PEP produced a significant afternoon surge of PRL in controls at weeks 1 and 2 but not week 3. Lesions of the corticomedial AMYG nuclei had no effect on basal PRL, but significantly blunted the afternoon surge occurring at weeks 1 and 2. The effect of a larger lesion encompassing a greater proportion of the corticomedial AMYG was examined in another group of rats at 6 weeks post-lesion and 2 weeeks after PEP injection. This lesion significantly decreased PRL levels compared to controls at 5 of 6 time periods examined over a 24-h period. The effect of this lesion on PRL secretion in non-estrogenized OVX rats was also examined. There was no difference in the low, non-fluctuating 24-h PRL levels of control and lesioned rats bled at 3 or 4 weeks post-lesion.
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The effects of suckling on serum prolactin levels and catecholamine concentrations and turnover were examined in several discrete brain regions. Turnover rates were assessed by using the synthesis inhibitor alpha-methyltyrosine (alpha-MT) in combination with microdissection techniques for the removal of individual brain regions and sensitive radioenzymatic assays for norepinephrine (NE) and dopaime (DA). Prolactin secretion was induced by mothers experiencing 6 h of pup removal with subsequent pup replacement. Suckling or the administration of alpha-MT to mothers resulted in a marked increase in circulating titers of prolactin. A decrease in steady-state NE concentrations in the anterior hypothalamus and a decrease in steady-state DA concentrations in the ventromedial nucleus were noted in suckled mothers. The comparison of relative rates of NE depletion after alpha-MT treatment revealed a suckling-induced increase in turnover in the ventromedial nucleus and a suckling-induced decrease in turnover in the anterior hypothalamus. Neither suckling nor alpha-MT treatment produced any changes in NE or DA turnover rates in the arcuate nucleus or median eminence. These findings demonstrate that suckling-induced activation of prolactin results in changes in noradrenergic processes in the ventromedial and anterior hypothalamic nuclei. This suggests an involvement of noradrenergic systems in suckling-induced prolactin release.
Prenatal stress significantly reduced the number of progeny born to 47% of the female offspring and significantly increased the incidence of low birthweight young. None of these litters survived by the tenth postpartum day when serum prolactin levels were significantly reduced. Upon autopsy, these females had twice as many uterine implantation sites than the number of fetuses they bore, suggesting that a) the reduced postpartum serum prolactin most likely was the cause rather than the effect of the neonatal mortality and b) major hormonal deficiencies (possibly gonadotropic-related) were present even before giving birth.
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In order to evaluate the spontaneous variability of prolactin (PRL) release in response to various stimuli applied repeatedly on different occasions, groups of 5 to 12 subjects each underwent consecutive identical tests with one of the following stimuli applied at 3-6 days' intervals: sulpiride (100 mg im), benserazide (50 mg po), insulin hypoglycaemia (0.1 U/kg b. w. iv) and arginine infusion (25 g iv in 30 min). When repeated in the same subjects, arginine and benserazide yielded superimposable results. In contrast to this, insulin hypoglycaemia yielded significantly lower PRL release, while the PRL response to the second sulpiride test was significantly higher than to the first one. When an interval of 10 days was left between two consecutive sulpiride tests, an identical PRL release was observed. These results indicate that arginine and benserazide are reproducible tests for PRL secretion and it is possible that the decreasing effect of insulin hypoglycaemia on PRL release is due to the stressful effect of the stimulus. Finally, sulpiride probably enhances both PRL release and synthesis thus making greater amounts of PRL available to a subsequent stimulus. Since some of the above stimuli are usual tools for the study of the neuroendocrine control of PRL secretion, our findings suggest that caution appears necessary in attributing to any (neuroactive) drug an effect which might be merely due to a lack of reproducibility of the stimulus employed.
The influence of oestrogen administered to the ovariectomized rat on the interaction between dopamine (DA) and thyrotrophin releasing hormone (TRH) on the release of radioimmunoassayable (RIA) and [3H]leucine incorporated into prolactin ([3H]PRL) was examined in vitro. Dopamine had a more marked suppressing effect on newly synthetized PRL (80%), as determined [3H]PRL, than on total PRL (50%), as determined by RIA-PRL. The administration of 5 micrograms of oestradiolbenzoate (OeB) for 7 days resulted in blocking the suppressing effect of DA when RIA-PRL was measured but not when [3H]PRL was measured. The administration of 5 micrograms of OeB enabled TRH to partially override the suppressing effect of DA and the degree of response was more marked when RIA-PRL was measured than when [3H]PRL was measured. The administration of 50 micrograms of OeB for 3 days enabled TRH to override the DA blockade of prolactin release to levels comparable to that of the control when RIA-PRL was measured but had little to no effect on [3H]PRL. The results are discussed in relation to the two storage pools of PRL in the pituitary and the data suggest that DA acts predominantly to suppress the newly synthetized, rapidly releasable pool. Oestrogen acts to block DA action on the older more stable PRL pool. The ability of TRH to override the DA blockade of PRL release depends upon the presence of oestrogen; here TRH acts predominantly on the older more stable pool of PRL. Oestrogen's action on disrupting the DA suppression of PRL release appears to be related to the time of day the hormone is administered subsequent to when the pituitary is exposed to DA in vitro.
The role of the pineal gland, olfactory bulbs and photoperiod in the regulation of the two daily surges of plasma prolactin in the pseudopregnant rat has been investigated. Pinealectomy had no effect on the surges of prolactin in pseudopregnant rats maintained on either a long (14 h light : 10 h darkness; 14L : 10D) or a short (2L : 22D) photoperiod, but olfactory bulbectomy decreased the nocturnal surge in animals maintained on 14L : 10D. This effect of bulbectomy was eliminated if the rats maintained on 14L : 10D were also pinealectomized. After cervical stimulation, bulbectomized rats maintained on a 2L : 22D photoperiod had nocturnal-type prolactin surges similar to those of intact rats maintained on the same photoperiod. These results indicate that the pineal gland andlength of photoperiod are not involved in the regulation of the surges of plasma prolactin in pseudopregnant rats but that the olfactory bulbs may enhance the nocturnal surge.
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