Nira Ben-Jonathan

Neuroendrocrine regulation of prolactin release

Article de synthese sur la regulation neuroendocrinienne de la liberation de la prolactine. Effet de la dopamine. Importance physiologique des facteurs de liberation de la prolactine

Pituitary lactotrophs endocrine, paracrine, juxtacrine, and autocrine interactions

The synthesis and release of PRL by the lactotrophs is subjected to multiple regulators that are classified into four categories: endocrine, paracrine, juxtacrine, and autocrine. Endocrine agents originate from the hypothalamus, gonads, and the posterior pituitary. Paracrine factors are produced by cells of the intermediate and anterior lobes. Juxtacrine transmitters arise from extracellular matrix and cells adjacent to the lactotrophs. Autocrine agents are synthesized by the lactotrophs themselves. Consequently, the overall secretory activity of the lactotrophs reflects a balance between local and distant releasing and inhibiting factors.

Plasma catecholamines in fetal and neonatal rats

Abstract During the last day of gestation, dopamine was higher in fetal than in maternal plasma whereas norepinephrine and epinephrine were similar. Immediately after birth, plasma norepinephrine and epinephrine fell to 10% of their levels in term fetuses, remained low in the second day of life and reached adult levels within one to two weeks. Plasma dopamine, however, did not reduce much after birth. The data are consistent with the predominance of the extra-adrenal chromaffin tissue in the fetus, its postnatal involution, and the delayed maturation of the adrenal medulla in the newborn.

Prolactin secretion by cultured anterior pituitary cells: influence of culture conditions and endocrine status of the pituitary donor

The characteristics of prolactin (PRL) secretion by cultured anterior pituitary cells in the presence and absence of catecholamines were studied. PRL secretion was markedly influenced by culture conditions such as cell density, culture duration and length of short-term incubation. Dopamine (DA) inhibited PRL release in a dose-dependent manner within a physiological range, and this inhibition was reversed by the stereospecific DA receptor antagonist (+)-butaclamol. In contrast, the inhibition of PRL secretion by norepinephrine (NE) required much higher doses and lacked specificity. Cells obtained from male donors had the lowest basal PRL secretion and were the least responsive to DA inhibition, whereas those obtained from females in late pregnancy had the highest basal PRL secretion and were the most sensitive to DA.

Chronic Posterior Pituitary Lobectomy: Prolonged Elevation of Plasma Prolactin and Interruption of Cyclicity

We previously reported that the posterior pituitary dopaminergic system participates in the inhibition of prolactin (PRL) secretion in both male and lactating female rats. However, posterior pituitary lobectomy (Lobex) of urethane-anesthetized cycling rats resulted in an elevation in plasma PRL for a short time only. This raises a question regarding the importance of input from the posterior pituitary to the control of PRL secretion during the estrous cycle. The objectives of this study were to examine the chronic effects of Lobex on plasma PRL levels in conscious rats and to determine whether the absence of input from the posterior pituitary interferes with estrous cyclicity. Lobex or sham lobectomy were performed under Brevital anesthesia in estrous rats. Blood was collected from jugular cannula at hourly intervals on the day of surgery and at 09.00, 13.00, and 17.00 h during the following 4 days. Daily water consumption and vaginal cyclicity were monitored for 14 and 20 days, respectively. Within 2 h after Lobex, the plasma PRL levels rose 3- to 4-fold and remained elevated for 3 days before declining to near control levels on the 4th day. None of the Lobex rats resumed cyclicity within 3-4 days, 50% had an interruption of cyclicity for 4-10 days, and the remainder were noncyclic for more than 11 days. Upon resumption of cyclicity, Lobex rats had 11.3 +/- 0.4 oviductal ova which is within the normal range for intact ovulating rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential Alterations in Dopamine Turnover Rates in the Stalk-Median Eminence and Posterior Pituitary during the Preovulatory Prolactin Surge

The relative contributions of dopamine (DA) and prolactin-releasing factor (PRF) in generating the preovulatory prolactin (PRL) surge were investigated. Immature female rats were injected with pregnant mares serum gonadotropin (PMSG) on day 28. Jugular blood was collected hourly on days 30 and 31. PRL levels were low in the morning of day 30, rose 10-12 times to peak levels from 14.00 to 16.00 h, reached a prolonged plateau from 18.00 to 24.00 h, and reduced to basal levels in the morning of day 31. All PMSG-treated rats ovulated an average of 13-14 ova. PRL levels in age-matched control rats were low throughout this time, and no oviductal ova were present. DA turnover rates in the stalk-median eminence (SME) and posterior pituitary (PP) were determined from the decline in tissue DA after injecting alpha-methyl-p-tyrosine (alpha-MPT), a competitive inhibitor of tyrosine hydroxylase. DA turnover rates increased or were unaltered in the SME and PP, respectively, during the peak PRL phase as compared to presurge rates. In contrast, DA turnover rates were significantly reduced in both tissues during the plateau phase. The turnover rate in the SME, but not the PP, was increased in the morning of day 31. DA turnover rates in control rats never changed. Injection of alpha-MPT to PMSG-treated rats increased PRL levels at all times examined except during the plateau phase. Blood PRL levels were also determined in PMSG-treated rats following posterior pituitary lobectomy or sham lobectomy. The PRL surge was similar in both groups and all rats ovulated.(ABSTRACT TRUNCATED AT 250 WORDS)

Estradiol-induced prolactinomas: differential effects on dopamine in posterior pituitary and median eminence

Prolactin release is inhibited by dopamine and stimulated by estradiol. Dopamine is released from nerve terminals in the median eminence and posterior pituitary. Estradiol may act directly on the anterior pituitary or by modulating the two dopaminergic systems. Estradiol treatment induces the formation of prolactinomas in Fischer 334 rats. Therefore, this strain was chosen as the experimental model. The first objective was to determine whether estradiol differentially regulates the two dopaminergic systems. The second objective was to explore whether the anterior pituitary in estradiol-treated rats acquires the capability for de novo synthesis of dopamine. Rats were ovariectomized and implanted with estradiol capsules (OVEX + E2). Controls were untreated ovariectomized rats (OVEX). Three weeks thereafter, rats were killed. Anterior and posterior pituitaries and medial basal hypothalami (MBH) were removed and individually incubated for 60 min in Hanks balanced salt solution containing 10 microCi [3H-]tyrosine. The median eminence was then dissected from the MBH. Tissues were homogenized in perchloric acid and the supernatant fluids were extracted with alumina. Both endogenous and tritiated dopamine were simultaneously quantitated by HPLC. Prolactinoma formation in OVEX + E2 rats was confirmed by dramatic rise (50-fold) in plasma prolactin levels and marked enlargement (3-fold) of the anterior pituitary. Estradiol treatment caused a significant 60% reduction in both dopamine content and synthesis in the median eminence. In contrast, estradiol treatment affected neither dopamine content nor synthesis in the posterior pituitary. There was no evidence for de novo synthesis of dopamine in anterior pituitaries from either OVEX or OVEX + E2 rats. We conclude that the two dopaminergic systems which regulate prolactin secretion, exhibit a differential response to estradiol.

Ontogeny of Prolactin Releasing and Inhibiting Activities in the Posterior Pituitary of Male Rats

Plasma PRL levels in male rats are highest during the peripubertal period. We previously reported that the posterior pituitary (PP) contains a potent PRL-releasing factor (PRF), a trypsin-insensitive small peptide which is distinct from known PRL secretagogues. The objectives were to determine the ontogeny of PRF activity in the PP as well as age-related alterations in anterior pituitary responsiveness to PRF. We also explored if the PP contains a nondopaminergic PRL-inhibiting factor (PIF). PRF/PIF activities were assessed by the ability of PP extracts to alter PRL release from cultured anterior pituitary cells. The PP were extracted with perchloric acid and lyophilized, thus eliminating endogenous dopamine. PRF activity in PP extracts from 10- and 20 day-old (d) rats was very low, increased gradually in 30d and 40d rats, and remained unchanged in adult (90d) rats. In a second experiment, age-related changes in anterior pituitary responsiveness to PP extracts from adult rats and to TRH were determined. The responsiveness of anterior pituitary cells from 10d rats to PRF was low, increased dramatically in cells from 20d rats, and was reduced in cells from 30d and adult rats. The responsiveness to TRH was highest in cells from 10d rats. In a third experiment, anterior pituitary responsiveness to age-matched PP extracts was assessed. Only PIF activity was observed when PP extracts from 10d rats were incubated with anterior pituitary cells from 10d rats. In contrast, PP extracts from 20d, 30d and adult rats exhibited only PRF activity when incubated with age-matched cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential Effects of Pituitary Stalk-Section on Posterior Pituitary and Hypothalamic Contents of Prolactin-Releasing Factor, Oxytocin, Dopamine and Beta-Endorphin

We have recently shown that the posterior pituitary (neurointermediate lobe) contains a potent prolactin (PRL)-releasing factor (PRF) which is distinct from known PRL secretagogues. Posterior pituitary PRF appears to be a small peptide of an unknown cellular origin. Using pituitary stalk-sectioned (SS) male rats, the objectives of this study were: (1) to determine if PRF is transported from the hypothalamus or is synthesized within the pituitary gland, and (2) to compare changes in PRF activity with alterations in the posterior pituitary content of beta-endorphin (beta-END), oxytocin (OXY), and dopamine (DA). One or two weeks following pituitary SS or sham surgery (SHAM), acid extracts of the posterior pituitary and medial basal hypothalamus (MBH) were analyzed for their hormone content. PRF activity was assessed by determining the stimulation of PRL secretion from perifused anterior pituitary cells, DA was measured by HPLC, and OXY and beta-END levels were determined by RIAs. OXY and DA concentrations in the posterior pituitary were reduced more than 95% at both 1 and 2 weeks after SS. PRF activity in the posterior pituitary was significantly reduced by 75 and 90%, 1 and 2 weeks after SS, respectively. In contrast, beta-END levels in the posterior pituitary at these times increased 20 and 60%, as compared to SHAM rats. Unlike the posterior pituitary, OXY levels in the MBH increased 123% 1 week following SS, and 1,260% at 2 weeks. These increases may reflect the accumulation of OXY-containing secretory vesicles in the severed nerves. DA concentrations in the MBH showed a biphasic pattern. DA levels were initially decreased by 70%, and then increased, but remained 30% below SHAM levels. The reason for these alterations in DA levels is not clear.(ABSTRACT TRUNCATED AT 250 WORDS)

Predominance of l-dopa in fetal plasma and the amniotic fluid during late gestation in the rat

The purpose of this study was to reevaluate catecholamine distribution in fetal and maternal compartments during late gestation in the rat. Fetal and maternal plasma and amniotic fluid were collected from anesthetized rats on consecutive days from day 17 to day 22, the day of parturition. The fluid was analyzed for dihydroxyphenylalanine (L-dopa), dopamine, norepinephrine, and epinephrine by radioenzymatic assays. Amniotic fluid volume was determined by a direct weighing method. L-Dopa concentrations constituted approximately 50% of total fetal plasma catecholamines and were significantly higher in fetal than in maternal circulation. Dopamine concentrations in fetal plasma were tenfold lower than those of L-dopa but were also significantly higher in fetal than in maternal plasma; norepinephrine levels were similar in both. Maternal plasma epinephrine levels remained relatively constant, whereas fetal epinephrine levels increased fiftyfold from day 17 to day 22. L-Dopa concentrations in the amniotic fluid were tenfold higher than those of dopamine, and the concentrations of both increased markedly during the last 2 days of gestation. However, this apparent rise could be attributed to the concomitant fivefold reduction in the amniotic fluid volume observed at this time. It is concluded that L-dopa is the predominant catecholamine in both the fetal plasma and the amniotic fluid during late gestation in the rat. At the present time, neither the source nor the possible physiologic functions of L-dopa during fetal life are known.