Biomedical subjects

M Selmanoff

Publications and source records attributed to M Selmanoff.

At least 37 records · Page 2Linked to original sources

PubMed1993

Graded hyperprolactinemia first suppresses LH pulse frequency and then pulse amplitude in castrated male rats.

We recently demonstrated that the ability of administered ovine prolactin (oPRL) to suppress postcastration LH secretion exhibited a clear dose dependency. In the present study, we determined whether this dose-related suppression of mean LH levels resulted from differential, dose-related effects of oPRL on LH pulse amplitude and pulse frequency. Adult male rats were orchiectomized and adrenalectomized, implanted with an atrial cannula and a 50% corticosterone pellet, and injected every 12 h with oPRL or its polyvinylpyrrolidone (PVP) vehicle beginning at time 0. Increasing doses of oPRL (600, 2,400 and 9,600 micrograms/injection) suppressed mean LH titers in a dose-dependent manner at 48 h postcastration. The mean maximal LH increments (delta LH) to two LHRH challenges at two doses (5 and 25 ng LHRH/100 g body weight) were unaffected by oPRL administration. The 600 micrograms oPRL dose significantly suppressed mean LH values by markedly increasing the inter-peak interval (42.6 +/- 6.7 min) compared with controls (26.6 +/- 0.2 min) since the pulse amplitude was unaffected (2.8 +/- 0.4 vs. 2.6 +/- 0.4 ng/ml, respectively). The two higher oPRL doses suppressed both LH pulse frequency and pulse amplitude. Hence, elevated PRL levels first suppress LH pulse frequency and then, at higher concentrations, pulse amplitude as well. Presuming that LHRH pulses result from ensemble firing of all or a significant proportion of the LHRH neurons projecting to the median eminence, the present data suggest that the neurons first affected by elevated PRL levels are the ones responsible for this frequency of this coordinated firing.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗

PubMed1993

Hyperprolactinemia suppresses the luteinizing hormone responses to N-methyl-D-aspartate, epinephrine, and neuropeptide-Y in male rats.

This study characterizes the responses of LHRH neurons to N-methyl-D-aspartate (NMDA), norepinephrine, epinephrine (E), and neuropeptide-Y (NPY), as evidenced indirectly by the measurement of circulating LH titers, and investigates whether neurons using these compounds as neurotransmitters might be involved in mediating hyperprolactinemic (HP) suppression of LH release. Male rats were orchidectomized, adrenalectomized, and implanted with a testosterone-containing Silastic capsule, a 50% corticosterone pellet, and third cerebroventricular and right atrial cannulae at time zero. Rats received sc injections of ovine PRL (2400 micrograms/250 microliters) in a polyvinylpyrrolidone depot or vehicle every 12 h for 48 h when experiments were performed. The mean maximal LH increments (delta LH) in response to two doses of LHRH (0.4 and 0.8 ng/100 g BW) were not altered in HP rats, indicating that ovine PRL did not cause a change in pituitary responsiveness. NMDA (20 mg/kg BW, iv)-induced LH release peaked 5 min after injection. The delta LH (0-5 min) in HP rats was suppressed by 53% compared with the control value. Epinephrine [5, 10, and 15 micrograms/2 microliters, intracerebroventricularly (icv)], but not norepinephrine (20 and 40 micrograms/2 microliters, icv), produced dose-dependent LH responses that peaked at 10 min. The delta LH (0-10 min) in HP rats in response to 10 micrograms/2 microliters E was suppressed by 68% compared with the control value. Two doses of NPY (2 and 10 micrograms/2 microliters, icv) produced dose-dependent LH increments that peaked at 10 min. In HP rats, the delta LH (0-10 min) in response to 10 micrograms/2 microliters NPY was suppressed 52% compared with the control value. The combined administration of E (10 or 16 micrograms) and NPY (5 or 10 micrograms) produced mean maximal LH responses that significantly exceeded the additive responses of these compounds individually. This synergistic effect may be mediated by separate adrenergic and NPYergic afferents to the LHRH neurons or may, in fact, reflect corelease of these two neurotransmitters from the same neurons. The LH responses to NMDA, E, and NPY were all inhibited in HP rats. This suggests that elevated PRL levels act on the LHRH neurons, either directly or indirectly through an inhibitory afferent neuronal system, to decrease their responsivity to all stimuli.

Adrenalectomy↗

PubMed1993

Differential effects of adrenalectomy on the prolactin-induced suppression of LH and FSH secretion after castration in male rats.

Hyperprolactinaemia inhibits gonadotrophin secretion in males and females of many species. The aim of this study was to determine the role of the adrenal gland in mediating the inhibitory effects of prolactin by contrasting the effects of acute hyperprolactinaemia on LH and FSH secretion in adrenal-intact and adrenalectomized rats with and without physiological corticosterone replacement. Adult male rats were administered purified ovine prolactin every 12 h (2.4 mg per injection s.c.) beginning at the time of castration. Blood samples were collected every 3 h for 36 h, then every 12 h until 10 days after castration. Ovine prolactin significantly reduced LH secretion in all groups from approximately 15 to 48 h after castration. In contrast, plasma FSH concentrations were reduced by ovine prolactin from 21 to 48 h only in the adrenal-intact rats and not in the adrenalectomized or adrenalectomized plus corticosterone groups. In all groups, ovine prolactin inhibited endogenous prolactin secretion in rats by short-loop autofeedback as soon as 3 h after the first ovine prolactin injection and throughout the 10 days of the study. Adrenalectomy per se, with or without corticosterone replacement, also had a differential effect on LH and FSH secretion after castration, causing only a transient delay in the rise in LH after castration, but inducing a significant and long-lasting inhibition of FSH secretion. The results demonstrate that ovine prolactin-induced suppression of LH secretion after castration occurs with or without the adrenal glands. Suppression of FSH secretion after castration by ovine prolactin, however, may involve an adrenal component.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

PubMed1991

Tyrosine hydroxylase and POMC mRNA in the arcuate region are increased by castration and hyperprolactinemia.

We have examined the changes which occur in neuronal expression of tyrosine hydroxylase (TH) and proopiomelanocortin (POMC) mRNA in response to castration and hyperprolactinemia (HP) in male rats. Steady-state mRNA levels were determined by quantitative in situ hybridization histochemistry (ISHH) using 35S-labeled synthetic 48-base oligodeoxynucleotide probes. Castration produced a 27% increase in TH mRNA in the periventricular and arcuate nuclei. PRL-exposed rats exhibited a further 27% increase in the level of TH mRNA and a striking 48% increase in POMC mRNA in periarcuate region cell bodies. These results indicate that gonadal steroids and PRL are involved, either directly or indirectly, in regulating the biosynthesis of TH and POMC in the hypothalamus.

Analysis of Variance↗

PubMed1991

Dose-dependent suppression of postcastration luteinizing hormone secretion exerted by exogenous prolactin administration in male rats: a model for studying hyperprolactinemic hypogonadism.

We examined the inhibitory effects of acute hyperprolactinemia on the postcastration rise in mean luteinizing hormone (LH) levels in adult male rats. The animals were administered purified ovine prolactin (oPRL) subcutaneously in a polyvinyl-pyrrolidone depot every 12 h for 96 h, beginning at the time of castration. oPRL suppressed postcastration LH secretion from 24 to 72 h when the effect spontaneously reversed in the face of elevated oPRL levels. oPRL suppressed postcastration LH secretion in a graded, dose-dependent fashion. The rats were administered increasing doses of oPRL and studied 48 h later, a time of maximal LH suppression. The first significant inhibition began in the high physiological range (about 200 ng/ml) and continued into the pathophysiological tumor range (about 2,500 ng/ml) of circulating oPRL levels. The highest oPRL levels markedly suppressed postcastration LH release. Autoregulatory feedback of oPRL on endogenous rat PRL secretion was examined in the dose-response study. It was striking to discover that PRL autofeedback appeared regulated as a threshold instead of a graded dose response and, more importantly, that the oPRL dose which produced the first significant suppression of LH secretion was the same dose which exerted PRL autofeedback. These findings indicate that postcastration LH secretion is inhibited by circulating PRL titers (about 200 ng/ml) which are above basal and stress-induced levels, but are within the range encountered during pregnancy, pseudopregnancy, and lactation. In addition, a common hypothalamic mechanism (perhaps dopaminergic), activated by elevated oPRL levels in this range, may inhibit both LH and rat PRL secretion.

Adrenalectomy↗

PubMed1991

Effects of tumor-induced hyperprolactinemia on LH secretion following stimulation of the medial preoptic area, pituitary responsiveness and the estrogen-induced LH surge.

In the present study we utilized the 7315a PRL- and ACTH-secreting tumor to induce a hyperprolactinemic (HP) state sufficient to profoundly suppress the postcastration LH rise in female rats. Tumor-induced prolactin levels which ranged 2,000-3,000 ng/ml substantially reduced the LH rise in both ovariectomized (OVX) and OVX + estradiol-17 beta (E2)-treated rats. Bilateral electrochemical stimulation (ECS, 100 microA DC for 60 s) of the ventral diagonal band of Broca-medial preoptic area (DBB-MPOA) resulted in comparable LH responses in control and HP rats in the presence of absence of estradiol. Transient decreases in PRL release occurred following ECS of the DBB-MPOA. Pituitary responsiveness was assessed with two LHRH challenges spaced 60 min apart at doses of 25 and 50 ng LHRH/100 g body weight. The mean maximal LH increments (delta LH) to some of these LHRH challenges were decreased in HP rats. Finally, the LH surge induced in the afternoon in OVX + E2-treated rats was diminished 71% by the presence of the PRL-secreting tumor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Single cell levels of hypothalamic messenger ribonucleic acid encoding luteinizing hormone-releasing hormone in intact, castrated, and hyperprolactinemic male rats.

We have examined the changes that occur in neuronal expression of LHRH mRNA in response to castration and hyperprolactinemia in male rats. Single cell levels of LHRH mRNA were determined by quantitative in situ hybridization histochemistry using an 35S-labeled synthetic 48-base oligodeoxynucleotide probe and quantitative autoradiography. Nine days postcastration, a 10.4-fold increase in mean plasma LH titers was observed which was associated with significantly increased LHRH mRNA in rostral hypothalamic neuronal cell bodies. Both increases were blocked in rats rendered hyperprolactinemic by the presence of the 7315a PRL-secreting pituitary tumor. The location and number of neurons expressing LHRH mRNA were unchanged, indicating that these differences were attributable to amounts of mRNA expressed per neuron. Experimental differences occurred in LHRH perikarya situated throughout the rostral hypothalamus from the organum vasculosum of the lamina terminalis to the caudal extent of the medial preoptic nucleus. These results suggest that gonadal steroids and PRL are involved, either directly or indirectly, in regulating the biosynthesis of LHRH in the rostral hypothalamus.

Animals↗

PubMed1990

Changes in the kinetics of [3H]dopamine release from median eminence and striatal synaptosomes during aging.

The release of preaccumulated tritium-labeled dopamine [( 3H]DA) was examined in isolated nerve terminals (synaptosomes) prepared from the median eminence (ME) and corpus striatum (CS) of young (2-3 months), middle-aged (11-12 months), and old (19-21 months) male rats. Fractional release of [3H]DA was measured over 1- to 10-sec time intervals under basal (5 mM K+) and depolarizing (75 mM K+) conditions in the presence of calcium. No differences in the rate of basal efflux between the age groups were observed in either ME or CS preparations. Fast-phase evoked [3H]DA release (0-1 sec) from CS synaptosomes was unchanged from young to middle-aged, but was decreased in old preparations. These data demonstrate that the nigrostriatal nerve terminal has a diminished ability to respond fully to depolarizing stimuli in advanced age. Mean serum PRL levels in old rats were 2.3-fold greater than those in both young and middle-aged rats, while serum LH levels were decreased 2.0-fold in middle-aged and old compared with those in young rats. The fact that LH levels were already decreased in middle-aged rats while PRL levels had not yet increased suggests that decreased gonadotropin titers in old rats do not result from the coincident hyperprolactinemia. In ME synaptosomes, depolarization-induced [3H]DA release was decreased at all time points in middle-aged preparations compared to that in young preparations. The reduced fractional release from the middle-aged ME synaptosomes was due to a depressed rate of release during the initial second of depolarization. Evoked release from ME terminals of old rats was comparable to that measured in the young group. Thus, there occurred an age-related biphasic change in the initial rate of evoked DA release from ME synaptosomes. Diminished response of ME dopaminergic terminals to depolarizing stimuli during middle age may be important in the later development of hyperprolactinemia in aging male rats. The increased PRL available for feedback on the tuberoinfundlbular dopaminergic neurons may, in turn, be associated with the apparent recovery of evoked [3H]DA release from ME synaptosomes of old rats.

Aging↗

PubMed1988

Phorbol esters potentiate rapid dopamine release from median eminence and striatal synaptosomes.

In the present study, we investigated the ability of phorbol esters to potentiate Ca2+-dependent depolarization-induced release of tritium-labeled dopamine ([3H]DA) from median eminence and striatal synaptosomes. Phorbol esters potentiated [3H]DA release in a concentration-dependent manner in both kinds of dopaminergic nerve terminals and with a potency series similar to that reported for stimulation of protein kinase-C (PKC) activity in other cell systems. Evoked [3H]DA release was increased by 12-O-tetradecanoylphorbol-13-acetate (TPA; 10(-7) M) after 1, 3, 5, and 10 sec of depolarization. The effect of TPA was suppressed by sphingosine, a PKC inhibitor. TPA enhanced [3H]DA release evoked by high K+, veratridine or the Ca2+ ionophore A23187. Phorbol ester potentiation was found to be depolarization dependent, as it was present from 30-75 mM, but not at 5-20 mM external K+. Potentiation was seen at all external Ca2+ concentrations studied between 0.01-3 mM. However, in the absence of external free Ca2+ (i.e. with 0.1 mM EGTA), the phorbol effect was not present. These data indicate that an increase in intrasynaptosomal Ca2+ concentration is necessary for the enhancement of [3H]DA release by phorbol esters to occur. The combination of TPA and the Ca2+ ionophore A23187 does not show the marked synergism observed in some other systems, that is maximal release was not reinstated. This suggests that in dopaminergic nerve terminals, activation of PKC has a modulatory, rather than a mediating, effect on release. Recently, we have shown that hyperprolactinemia stimulated [3H]DA release from median eminence synaptosomes by an external Ca2+-independent mechanism which might involve the PKC pathway. However, in the present work we found that the TPA and PRL effects on evoked [3H]DA release were additive, suggesting that two independent mechanisms are involved. A marked difference in the sensitivity of median eminence and striatal synaptosomes to calcium ionophore was discovered. The concentration of A23187 required to support significant [3H]DA release from median eminence synaptosomes was 3-fold greater than that in striatal synaptosomes. This suggests that some difference in calcium homeostatic processes exists, such as a higher resting striatal Ca2+ concentration, in these two kinds of dopaminergic nerve terminals. These data support the hypothesis that PKC activation potentiates the intrasynaptosomal stimulus-secretion coupling mechanism(s) and that nigrostriatal and tuberoinfundibular dopaminergic nerve terminals are affected by phorbol esters in a similar manner.

Animals↗

PubMed1988

Selective effects of hyperprolactinemia on in vitro dopamine release from median eminence synaptosomes.

Prolactin is thought to exert an autoregulatory, negative feedback effect on its own secretion via stimulation of the tuberoinfundibular dopaminergic (TIDA) neurons. To investigate possible mechanisms involved in this feedback, the effects of experimentally induced hyperprolactinemia on the release of 3H-dopamine (3H-DA) were studied in nerve terminals (synaptosomes) isolated from rat median eminence (ME), the TIDA neuronal projection field. Synaptosomes were prepared from adult male rats treated with ovine prolactin (oPRL) or the vehicle for 48 hr. Synaptosomes were incubated in 0.1 microM 3H-DA at 30 degrees C until steady-state conditions were achieved, and then release of the preaccumulated transmitter was measured over 1-20 sec time intervals under basal and depolarizing conditions. Release of 3H-DA elicited by depolarization of the terminals was significantly greater in ME synaptosomes prepared from oPRL-treated animals as compared with preparations from controls. This effect of the hyperprolactinemia appeared to be specific to the TIDA neurons since oPRL treatment did not result in increased evoked release of 3H-DA from terminals prepared from the mesolimbic, tuberohypophyseal, or nigrostriatal dopaminergic neurons. Basal efflux in all preparations was not changed from controls. The increased evoked release in oPRL-treated ME occurred when depolarization was induced either with high external [KCl] or veratridine. The enhanced 3H-DA efflux was evident during depolarization over a wide range of external calcium concentrations (0.01-3.0 mM), in the presence of 20 nM Ni2+ to block Ca2+ influx through voltage-gated channels, or when all external Ca2+ had been chelated, indicating that this effect of oPRL involves DA released through a mechanism independent of external calcium.

Animals↗

PubMed1987

Distribution of 3,4-dihydroxyphenylacetic acid (DOPAC) and 3,4-dihydroxyphenylglycol (DOPEG) in microdissected brain structures and the pituitary gland: metabolite changes in the median eminence in response to hyperprolactinemia and suckling.

Dopamine (DA), norepinephrine (NE), epinephrine (E), 3,4-dihydroxyphenylglycol (DOPEG) and dihydroxyphenylacetic acid (DOPAC) were determined simultaneously by a radioenzymatic, thin-layer chromatographic assay able to detect 1-10 pg of the parent compounds and 80-120 pg of their metabolites. A localization study of these compounds in 20 micro-dissected hypothalamic and limbic structures and the anterior and posterior pituitary glands of male rats was completed. DOPAC was detectable in 14 of 22 structures with the lowest DOPAC/DA ratio being found in the caudate nucleus (7.1%) and the highest in the medial aspect of the ventromedial nucleus of the hypothalamus (422.0%). There was a higher DOPAC/DA ratio in the lateral (21.5%) than in the medial (11.3%) portion of the median eminence suggesting that a greater portion of released DA in the medial median eminence enters the portal circulation. DOPEG was detectable in 6 of 22 structures with DOPEG/NE ratios ranging from 8% (interstitial nucleus of the stria terminalis, ventral aspect) to 32% (medial median eminence). A poor correlation exists between DOPAC and DA concentrations in the various brain regions while there was a stronger relationship between DOPEG and NE concentrations. Male rats were rendered hyper-prolactinemic for 48 hours with injections of ovine prolactin (oPRL) every 8 hours (4 mg/kg body weight sc). In such rats there was a suppression of endogenous rat PRL (rPRL) secretion, the DOPAC/DA ratio increased 2.2-fold in the medial (MEm) and 1.9-fold in the lateral median eminence (MEl), and the DA concentration in the anterior pituitary also increased 2.6-fold. In 10 day postpartum lactating rats, suckling produced marked increases in serum rPRL but no change in DOPAC/DA ratios in the ME or in the DA concentration in the anterior pituitary. The data reveal a wide range of DOPAC/DA ratios (7-422%) in brain regions containing cell bodies, axons and terminals of the different dopaminergic neuronal tracts in brain and pituitary. Considering the DOPAC/DA ratios in the MEm and MEl, it is suggested that a large perturbation of dopaminergic transmission produces a significant ratio change while a smaller perturbation is not detected by this index of neuronal metabolism.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1987

Rapid release of [3H]dopamine from median eminence and striatal synaptosomes.

Release of preaccumulated, tritium-labeled dopamine ([3H]DA) from preparations of isolated nerve terminals (synaptosomes) of rat median eminence (ME) and corpus striatum (CS) was examined over short time intervals (1-20 s). In both preparations, basal efflux of [3H]DA was linear with time. Depolarization with high K+ resulted in an initial rapid release of [3H]DA which stabilized by 20 s, whereas veratridine elicited an increased rate of release over basal levels that was linear over the first 20 s. The calculated rate constants of release for both the initial phase of K+- and the veratridine-stimulated release were approximately threefold greater in CS than in ME synaptosomes. The major component of the high K+-induced release of [3H]DA from both synaptosome preparations increased as a graded function of [Ca2+]o. However, a smaller component, independent of external Ca2+, existed in both ME and CS synaptosomes. Increasing the [Mg2+] in the external solution resulted in a right shift of both the [K+]o and the [Ca2+]o dose-response curves, consistent with actions of Mg2+ on screening surface membrane charges and blocking voltage-dependent Ca2+ channels. In all studies, steady-state uptake of the [3H]DA was about twofold greater into CS than into ME synaptosomes. Moreover, the fraction of incorporated [3H]DA released by stimulation from the CS was much greater than that released from ME synaptosomes. These data are consistent with differences between these two types of dopaminergic terminals with respect to packaging and/or distribution of the accumulated neurotransmitter in intraneuronal pools, as well as marked differences in the apparent kinetics of DA release.

Animals↗

PubMed1987

Effects of hyperprolactinemia on plasma prolactin and glucose and on local cerebral glucose utilization.

Elevated blood levels of prolactin increase the synthesis, turnover, and release of 3,4-dihydroxyphenylethylamine (dopamine) from the tuberoinfundibular dopaminergic neurons, which project to the median eminence. The present study examined whether hyperprolactinemia also increases local cerebral glucose utilization, as determined by the 2-deoxy-D-[1-14C]glucose method, in the median eminence and other brain structures. Adult male rats were given ovine prolactin (4 mg/kg) subcutaneously every 8 h for 48 h. This treatment exerted an autoregulatory feedback effect on endogenous rat prolactin secretion, as evidenced by decreased circulating levels of rat prolactin. Ovine prolactin treatment also decreased plasma glucose concentrations. However, in both partially immobilized and free-ranging rats, glucose utilization in brain structures containing tuberoinfundibular dopaminergic cell bodies (the arcuate nucleus) and terminals (the median eminence) was not affected by ovine prolactin treatment. Hyperprolactinemia was, however, associated with decreased glucose utilization in the medial forebrain bundle and the CA subfield of the dorsal hippocampus. The lack of a significant effect of prolactin treatment on glucose utilization in the median eminence indicates that the resolution of the deoxyglucose technique, as used here, is not adequate to detect the ovine prolactin-induced increase in tuberoinfundibular dopaminergic neuronal activity, that the median eminence does not utilize glucose as its primary energy substrate, or that ovine prolactin treatment causes a counterbalancing decrease in the activity of other neurons projecting to the median eminence.

Animals↗

PubMed1986

Suckling-induced prolactin release is suppressed by naloxone and simulated by beta-endorphin.

The role that opiate peptides play in suckling-induced prolactin (PRL) release was examined in 10-day postpartum lactating rats. The opiate receptor antagonist naloxone (NAL) suppressed suckling-induced PRL release in a dose-dependent manner and a large dose abolished the response. These results suggest either that opiate neurons are situated in the neuronal pathway mediating this neuroendocrine response, or alternatively, that opiate neurons are situated such that they can modulate neuronal transmission in this pathway. It is suggested that NAL blocks a tonic, inhibitory beta-endorphinergic input to the tuberoinfundibular dopaminergic (TIDA) neurons, hence, NAL administration in effect stimulates the TIDA neurons and in this way overrides the suckling response. Intravenous, bolus administration of beta-endorphin (beta-END) produced a PRL response that was similar to the suckling response in terms of latency of onset and duration while the magnitude of the beta-END-induced response was 2-fold greater than that produced by the suckling stimulus. NAL abolished beta-END-induced PRL release at a much lower dose than that required to inhibit suckling-induced PRL release. This suggests that the neural mediation of the suckling response involves a mechanism in addition to the one inhibited by opiate receptor blockade.

Animals↗

PubMed1986

Hyperprolactinemia alters the frequency and amplitude of pulsatile luteinizing hormone secretion in the ovariectomized rat.

Studies were undertaken to examine the effects of hyperprolactinemia on the frequency and amplitude of pulses of LH, and determine if changes in pituitary sensitivity to LHRH were involved in the prolactin-induced suppression of LH secretion. Rats were bilaterally ovariectomized (day 0). Ovine prolactin (4 mg/kg body weight, subcutaneously) or vehicle was administered every 8 h beginning at 09.00 h on day 4 after ovariectomy and continuing until 09.00 h on day 6. On day 6, between 07.00 and 09.00 h all animals received a right atrial cannula, using ether anesthesia. In experiment I blood samples were taken at 10-min intervals beginning at 12.00 h on day 6, for a total of 180 min. To test the effect of hyperprolactinemia on pituitary responsiveness (experiment II) animals received an intravenous injection of LHRH (25 ng/100 g body weight) after the 180-min and again after the 240-min sample. Blood was drawn every 10 min for a total of 300 min. Serum was assayed for LH. Hyperprolactinemia altered the pattern of pulsatile secretion of LH. Treatment with ovine prolactin produced a decrease in both the frequency and amplitude of the LH pulses compared to values found in control animals. However, no differences in pituitary responsiveness between hyperprolactinemic and control animals were found at the dose of LHRH given. Thus, the prolactin-induced suppression of pulsatile secretion of LH was not apparently a result of alterations in the sensitivity of the pituitary to LHRH. From these studies we suggest that hyperprolactinemia directly affects a hypothalamic site which ultimately alters the LHRH pulse generator, thereby changing the secretion of LHRH.

Animals↗

PubMed1986

Inhibitory effects of exogenously induced hyperprolactinemia on the endogenous cyclic release of luteinizing hormone and prolactin in the estrogen-primed ovariectomized rat.

The inhibitory effects of acute hyperprolactinemia on the cyclic release of LH and PRL were examined in the ovariectomized estradiol-treated rat. In Exp 1, animals were ovariectomized (day 0) and received sc injections of ovine (o) PRL (4 mg/kg BW) or vehicle beginning at 0900 h on day 4, 6, or 7 postovariectomy and continuing every 8 h until 0900 h on day 9. All animals were given Silastic capsules containing estradiol (E2) on day 7, were cannulated via the external jugular vein on day 8, and were bled at 0900 and 1030 h and at hourly intervals between 1200-1800 h on day 9. No effect of oPRL treatment on the cyclic release of LH was seen in 1-week ovariectomized rats regardless of the duration of PRL treatment. The endogenous rat PRL surge was attenuated by treatment with oPRL. In Exp 2, animals were ovariectomized (day 0) and, beginning on day 11 or 14 postovariectomy, received sc injections of oPRL or vehicle every 8 h until 0900 h on day 16. On day 14, animals received Silastic E2 capsules. The following day (day 15), the external jugular vein was cannulated, and at 1800 h, E2 capsules were removed from half of the rats. On day 16, rats were bled at the times outlined in Exp 1. When E2 levels were maintained by the continuous presence of an E2 capsule, hyperprolactinemia did not suppress the cyclic release of LH and only attenuated or shifted the timing of the rat PRL surge. In marked contrast, when E2 stimulation was discontinuous, oPRL abolished the steroid-induced LH surge in all animals treated with oPRL beginning on day 11 and in 57% of the animals treated beginning on day 14. Treatment with oPRL abolished the endogenous PRL surge in all animals regardless of the duration of PRL exposure. In conclusion, oPRL-induced hyperprolactinemia can inhibit E2-induced LH and PRL surges in long term ovariectomized rats under conditions of discontinuous E2 exposure. In contrast, when estrogen levels are maintained, hyperprolactinemia had no effect on the LH surge and only attenuated or shifted the timing of the endogenous PRL surge. Thus, the long term ovariectomized rat receiving discontinuous E2 provides a model that is particularly suited for the study of the possible neural mechanisms by which PRL inhibits cyclic release of LH.

Animals↗

PubMed1985

Suckling decreases dopamine turnover in both medial and lateral aspects of the median eminence in the rat.

The effect of suckling on dopamine (DA) turnover was studied in the medial and lateral aspects of the median eminence. In 10-day postpartum lactating rats suckling decreased DA turnover 2.2-fold in the medial and 2.1-fold in the lateral median eminence. Norepinephrine turnover did not differ in suckled and non-suckled rats. These results are consistent with the hypothesis that decreased DA release is a component of the neuroendocrine reflex mediating suckling-induced prolactin release. The results further indicate that dopaminergic neurons distributing to both medial and lateral aspects of the median eminence are involved in the suckling response.

Animals↗

PubMed1985

Rapid effects of hyperprolactinemia on basal prolactin secretion and dopamine turnover in the medial and lateral median eminence.

Subcutaneous injections of ovine PRL (oPRL; 4 mg/kg) were used to study the negative feedback of PRL on its own secretion in the adult male rat. A single injection of oPRL significantly suppressed the endogenous secretion of rat PRL within 3-4 h, an effect that persisted until the oPRL was substantially cleared from the circulation some 4-6 h later. In rats injected every 8 h, rat PRL levels were suppressed for 48 h, while LH titers increased significantly at some time points, and FSH levels varied in the same direction as LH. LHRH concentrations in 10 brain structures containing cell bodies, axons, and terminal boutons were not affected by 48 h of oPRL treatment. Dopamine turnover in both medial and lateral aspects of the median eminence increased as early as 2 h after the first oPRL injection and remained elevated after 10 and 26 h of oPRL exposure. The results are consistent with the hypothesis that the tuberoinfundibular dopamine neurons mediate the negative feedback action of PRL on its own secretion. Further, under these experimental conditions, neurons projecting to both medial and lateral aspects of the median eminence are equally sensitive to elevated PRL levels.

Animals↗