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Biomedical subjects

F Mena

Publications and source records attributed to F Mena.

At least 37 records · Page 2Linked to original sources
PubMed1989

Regulation of prolactin secretion by dopamine and thyrotropin-releasing hormone in lactating rat adenohypophyses: influence of intracellular age of the hormone.

We studied the effect of dopamine (DA) on the rate of processing of PRL after biosynthesis and, with TRH, on the secretion of PRL of different intracellular ages. In these studies anterior pituitary (AP) PRL of lactating rats was pulse labeled either in vivo with [3H]leucine (3 microCi/g BW, injected iv 0.2, 1, 4, 8, 16, or 24 h before removing the AP for incubation) or in vitro with [3H]- or [14C]leucine (5 microCi/ml Krebs-Ringer bicarbonate buffer for 5 min), followed by a chase period of 15-240 min of AP fragments in medium 199. Also, to determine if endogenous DA influenced PRL synthesis, the rate of [14C]-leucine incorporation into PRL was determined in AP fragments from alpha-methyl-p-tyrosine (alpha MpT)-pretreated (200 mg/kg BW) rats. Tissue and medium PRL levels were quantified by polyacrylamide gel electrophoresis densitometric and liquid scintillation techniques. In APs from alpha MpT-treated animals [14C]-leucine incorporation into PRL increased about 30% above control values after the 5-min pulse period, and the release of labeled PRL from alpha MpT-treated APs was about 80% higher than control values after 4 h of incubation. On the other hand, when DA (50 microM) was present in the incubation medium, AP concentrations and release of in vitro synthesized [3H]PRL were significantly decreased (45-55% compared to control values; P less than 0.001). The [3H]PRL concentration, but not that of total, i.e. unlabeled PRL, fell within the AP as the time from in vivo pulse labeling to removal of the pituitary gland increased from 8 to 24 h, thus suggesting that a loss of labeled hormone occurred as it aged within the gland. Also, it was found that biosynthesis and/or processing of PRL were markedly depressed in APs from rats whose pups were removed for 24 h. Under basal conditions, in vitro secretion of [3H]PRLs during the first 30-60 min of incubation consisted primarily of mature [3H]PRL, i.e. those labeled 4 and 8 h previously, whereas newly synthesized (labeled 0.2 and 1 h previously) and old [3H]PRL (labeled 16 and 24 h previously) were secreted at much lower rates. These data confirm previous in vivo and in vitro results on the sequential release of different age PRLs. DA (17 microM) had a significantly greater inhibitory effect on newly synthesized and older stored PRL than on PRL labeled 4-8 h previously. The converse was true with regard to the PRL stimulatory effects of TRH; it provoked greater stimulation of PRL labeled 4-8 h before incubation, thus suggesting an interdependence of the actions of DA or TRH with intracellular age of the hormone.

Animals↗
PubMed1987

Investigation into the role of dopamine and lysosomes in the impairment of prolactin transformation and release imposed by long periods of non-suckling in the rat.

The transformation of prolactin (PRL) within lactating rat hemipituitary glands incubated for 240 min and the release of the hormone into the incubation medium were progressively reduced by dopamine added to the medium over a 2.3-49 mumol/l range of concentration; the antilysosomal drug chloroquine did not alter these effects of dopamine. In related experiments, the short-term action of dopamine was manifested also upon in vitro transformation, repletion and release of in vivo labelled [3H]PRL, thus indicating that dopamine inhibits all phases of PRL secretion by the lactating rat anterior pituitary (AP). In other experiments, increasing the non-suckling period from 8 to 16 h reduced the pre-suckled concentration of PRL in the lactating rat AP, reduced the ability of the AP to transform PRL in response to suckling, and reduced the capability of the AP of such rats to secrete PRL in vitro. Injecting chloroquine (0.2 mmol/kg ip), haloperidol (0.27 mumol/kg ip) or providing 15-30 min of suckling midway during the 16-h non-suckling period restored each of these functions. Thus, frequent uncoupling of dopamine from its receptor appears necessary to prevent impairment of the suckling-induced transformation mechanism in the lactating rat AP and, presumably, to prevent PRL in the lactotrope from reaching an age where it becomes susceptible to lysosomal degradation.

Animals↗
PubMed1986

Comparison of plasma profiles of oxytocin and prolactin following suckling in the rat.

The purpose of these studies was to determine the effect of suckling on the plasma oxytocin (OT) concentration profile in conscious primiparous rats during midlactation. Comparisons were made with plasma prolactin (PRL) levels obtained in the same rats. OT levels in the majority of rats exhibited a single peak during the first 5-30 min, then fell rapidly during the course of a 45-min period of suckling. The plasma OT levels were sustained over a longer period in mothers suckling 8 rather than 6 pups; the amplitudes of the OT response were similar, however. By contrast, plasma PRL profiles indicated that a steady secretion of the hormone occurred throughout the suckling period, with suckling of 8 pups resulting in significantly higher plasma levels than suckling of 6 pups. A considerably greater increase in the peak plasma OT concentration resulted when hungry foster litters of 6 pups were suckled after the mothers' own 6 pups had been suckled. Plasma PRL levels during the two sucklings, though, were similar. The rapid onset of the OT response to suckling was seen more clearly in urethane-anesthetized rats following mammary nerve stimulation. Plasma OT levels rose to a peak within 5 s after the onset, then fell to prestimulus levels by the end of the 65-second stimulation period. These results suggest that different regulating mechanisms are involved in the secretory responses of OT and PRL to suckling and that different thresholds of activation are likely to exist for the two hormones.

Animals↗
PubMed1986

Thiol regulation of depletion-transformation and release of prolactin by the pituitary of the lactating rat.

We investigated the possibility that thiol-disulfide interchange mechanisms are involved in depletion-transformation (loss of tissue PRL detectability) and release of PRL from adenohypophyses (AP) of lactating rats. The influence of pH, bicarbonate, and Triton X-100 as well as thiol-related compounds on these processes was assessed. Tissue PRL was depleted-transformed by the use of three different conditions: 1) 30 min of suckling after 8 h of nonsuckling; 2) in vitro incubation of APs for 2 h; or 3) in vivo cysteamine (CSH) treatment. Lactating rats nonsuckled for 8 h served as controls (no depletion-transformation). The depletion-transformation phenomenon was unchanged by extraction with Tris-HCl-0.1% Triton X-100 buffers but reversed either by extraction with bicarbonate buffer (pH 8.2 or 9.7) or by incubation of pH 8.2 homogenates for 3 h at 37 C. Reduced glutathione (GSH) added to these homogenates further enhanced PRL detectability. At pH 6.5, however, incubation with or without GSH had the opposite effect and decreased PRL detectability. In AP incubations, depletion was increased in a dose- and time-dependent fashion by the aminothiol CSH, and by GSH, dithiothreitol, or mercaptoethanol but not sodium ascorbate. These agents also inhibited PRL release. Similar results were obtained after injection of CSH (20-120 mg/kg BW) 4 h before death. Depletion and release of PRL in incubated APs were prevented by iodoacetamide and N-ethylmaleimide (0.1-5 mM); GSH or CSH counteracted these effects. In contrast to the alkylating agents, oxidized glutathione and 5,5'-dithio-2-nitrobenzoic acid inhibited PRL depletion but stimulated PRL release. Thus, thiols and aminothiols may preferentially lead to depletion-transformation of PRL, whereas disulfides may inhibit depletion and facilitate PRL release. Although in some experiments increased depletion was dissociated from increased release, nonetheless the data support the concept that shifts in PRL detectability during depletion-transformation, repletion, and release involve thiol-disulfide interchange mechanisms.

Animals↗
PubMed1986

Reversal by thiols of dopamine-, stalk-median eminence-, and zinc-induced inhibition of prolactin transformation in adenohypophyses of lactating rats.

Depletion-transformation of PRL is a decrease in tissue PRL detectability which precedes and may often be required for increased PRL release. The present studies were designed to determine whether thiol-disulfide interchange mechanisms may be involved in PRL transformation and release by the pituitary of the lactating rat. Thirds of 8-h nonsuckled lactating rat adenohypophyses were incubated with or without thiols (reduced glutathione, the aminothiol cysteamine, or mercaptoethanol), in the presence of known inhibitors of transformation and release such as dopamine (DA), stalk median eminence (SME) extract, or Zn++. PRL concentrations in pre- and postincubated tissues, as well as the amount of released PRL, were determined by polyacrylamide gel electrophoresis and densitometry. In 30-min incubations without additions, 12-22% of the tissue PRL was depleted; however, in the presence of 17-50 microM DA, all doses of SME extracts tested (0.5-2.0 eq), or 0.1 mM Zn++, depletion was partially or totally prevented and PRL release was inhibited 25-60%. On the other hand, when thiols were added in addition to the above agents, a complete, dose-related, restoration of PRL depletion was obtained. In 120-min incubations, thiols similarly reversed the effects of 0.05 mM DA on depletion, but thiols did not reverse the inhibition of PRL release caused by DA, SME, or Zn++. Other data indicate that thiols alone may inhibit rat PRL release and also facilitate or induce PRL depletion; in bovine PRL granules, thiols reverse Zn++ inhibition of PRL release and detectability. These data suggest that thiol-disulfide interchange reactions may be importantly involved in both depletion-transformation and in secretion. The precise thiol sensitivity of the two processes does not appear identical, secretion being more sensitive to DA and less sensitive to thiols than depletion-transformation.

Animals↗
PubMed1985

Release of catecholamines follows suckling or electrical stimulation of mammary nerve in lactating rats.

The hypothesis that catecholamines may be released by mammary gland stimulation during lactation was tested by measuring, with an HPLC electrochemical method, plasma epinephrine (E) and norepinephrine (NE) concentrations during suckling in conscious rats and during electrical stimulation (pulses: 1 msec duration, 10/sec at 5-30 V) of the central end of a cut abdominal mammary nerve in urethane-anesthetized rats. Plasma E and NE concentrations were significantly elevated in two different strains of rats (Wistar and Holtzman) within 5 min of suckling. The concentration of E and NE did not change in control unsuckled rats during the same time period. As a complementary indication of sympathetic activation, it was observed that piloerection occurred during suckling. Plasma E levels (but not NE levels) increased significantly within 30 sec of a 2-min period of nerve stimulation in lactating rats on either day 7 or day 21 of lactation, as well as in nonlactating rats. The effect was significantly greater in nonlactating rats. The levels of E and NE were not altered after sham stimulation, whereas adrenalectomy abolished the rise in plasma E after mammary nerve stimulation. Blockade of the rise in plasma E also occurred after rapid injection of 100 microliters milk intraductally into each of two thoracic mammary glands, 15 sec before the onset of mammary nerve stimulation. These results show that E and NE can be released in response to suckling, and that activation of ductal mechanoreceptors may inhibit such release. These mechanisms may operate to regulate the rate of milk removal during suckling in the rat.

Adrenalectomy↗
PubMed1984

In-vivo and in-vitro secretion of prolactin by lactating rat adenohypophyses as a function of intracellular age.

Adenohypophysial prolactin of lactating rats was pulse-labelled by [3H]leucine injected i.v. at the time of removal of the pups. The [3H]prolactin concentration in the pituitary gland, analysed by polyacrylamide-gel electrophoresis, progressively fell as the time from labelling to removal of the pituitary gland increased from 8 to 24h, which suggests that there was a loss of hormone as it aged within the gland. Suckling effectively provoked the depletion-transformation of total and [3H]prolactin (extracted at pH 7.2) when applied after 8 h but not when applied after either 16 or 24 h after removing the pups. In rats whose pups were removed for 8 h, suckling also depleted-transformed [3H]prolactin labelled 4 h, but not that labelled 1 h before suckling. The pituitary glands of other lactating rats were labelled with [3H]leucine injected i.v. at various times before removing the glands and incubating them in medium 199. The secretion into the medium of [3H]prolactin labelled either 4, 8, 16 or 24 h beforehand was maximal during the first 30 min then declined from 30 to 240 min of incubation. However, secretion of prolactin labelled 1 h and 10 min beforehand reached a maximum after 0.5-1 h and 2 h of incubation respectively, then remained constant during the remainder of the 4-h incubation period. The total 4-h secretion of [3H]prolactin was greatest (65% of preincubation concentration) from those glands labelled 4 h before in contrast to those labelled 10 min (15%) or 1 (38%), 8 (34%), 16 (18%) or 24 h (26%) before incubation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1982

Latency and duration of the effects of bromocriptine and prolactin on milk secretion in lactating rabbits.

Milk yields were measured at 8h intervals in rabbits during early (days 11-14) and late (days 31-34) lactation. A single injection of 1 mg bromocriptine given to rabbits 30 min before sucking on days 11 or 31 caused a significant reduction in milk yield after approximately 8h. The depressant effect of the drug was then maintained over the next 24-36h. Recover of milk yield occurred in bromocriptine-treated rabbits during both early and late lactations 8-16h after a single injection of 3 mg prolactin. The recovery accelerated more in the rabbits in the early lactating group. Attainment of the maximal stimulatory effect occurred by 24h after prolactin injection during both early and late lactation although the improvement in milk yield lasted for a shorter period (8h compared with 24h) during late lactation compared with early lactation. These differences in response of the rabbit to prolactin during late lactation may contribute substantially to the declining milk yields characteristic of late lactation in this species.

Animals↗
PubMed1981

Autofeedback regulation of prolactin (PRL) secretion: effect of prolactin before suckling on the subsequent nursing-induced release of PRL in the lactating rat.

PRL can have an inhibitory effect upon its own release. The present investigation assessed quantitative and temporal relationships among exogenously raised systemic PRL concentrations, PRL discharged in situ, and PRL negative feedback control of PRL release. Lactating rats were administered PRL in amounts designed to increase systemic plasma PRL concentrations to levels that either exceed (3 mg ovine PRL injected sc) or fall within (five iv injections of 400 or 800 ng rat PRL given at 1-min intervals) the range of PRL concentrations normally produced by suckling stimulation. The 800-ng iv or 3-mg sc dose of PRL did not block the suckling-induced rise of plasma PRL concentration when given 30 min before suckling. When administered 4 h beforehand, however, 3 mg PRL reduced both the suckling- and ether-stimulated rises of plasma PRL. Although the 400- or 800-ng iv dose of PRL increased systemic plasma PRL concentrations to levels (280 and 389 ng/ml, respectively) that approximate those of the suckled rat, neither dose inhibited the suckling-induced release of PRL when given 4 h before nursing. These data indicate that high concentrations of PRL are required before PRL from the systemic circulation can activate PRL autoregulatory mechanisms, and that these mechanisms are not activated as an immediate response to rising plasma PRL titers. The suckling-induced release of PRL was also inhibited by 3 mg PRL given 16 h before nursing. The PRL discharged in situ by 15 min of nursing was not effective, however, in blocking the suckling-induced release of PRL 16 h later. Since large amounts of PRL can presumably reach PRL regulatory mechanisms during in situ release via retrograde pituitary secretion, we conclude that the functional significance of autofeedback control of PRL release may be limited to conditions where PRL secretion is prolonged or at an abnormally high rate.

Animals↗
PubMed1980

Effect of electrical stimulation of mammary nerve upon pituitary and plasma prolactin concentrations in anesthetized lactating rats.

A 50-70% depletion in the anterior pituitary concentration of PRL occurred within 5 min of electrical stimulation of a single abdominal mammary nerve of urethane-anesthetized lactating rats previously nonsuckled for 6-8 h. The stimulus parameters were: 1-msec pulses, 10-20/sec at 5-30 V applied 5 sec on and 10 sec off. The anterior pituitary concentration of PRL remained low for another 15-30 min after depletion, then repleted to prestimulus levels by the 90th min. The same pattern of depletion-repletion occurred when mammary nerve stimulation was applied for 5 min as when it was applied for 180 min. In other experiments, plasma PRL concentration rose swiftly and attained a maximal level, 4- to 5-fold in Wistar rats and 8- to 10-fold in Holtzman rats, above basal concentrations within 10-15 min of mammary nerve stimulation. The maximal level was sustained throughout the time the nerve was stimulated and for 45 min after the stimulation was stopped, i.e. the sustained secretion of PRL into the plasma occurred at the same time that depleted PRL was repleting. Ligation of both adrenals or iv injection of the beta-adrenergic blocker, propranolol, before stimulation of the nerve had no effect upon the plasma PRL profile in response to mammary nerve stimulation. These data indicate that mammary nerve stimulation mimics that of suckling upon depletion, repletion, and the release of PRL into the circulation and add further support to the hypothesis that these phases are independent processes.

Animals↗
PubMed1980

Evidence that the dopaminergic prolactin-inhibiting factor mechanism regulates only the depletion-transformation phase and not the release phase of prolactin secretion during suckling in the rat.

We have compared the effectiveness of stalk-median eminence (SME) extracts, dopamine, and bromocriptine (CB-154) in inhibiting the release of PRL into the plasma during suckling when injected before depletion with that when the injections were given after the pituitary stores of PRL had been depleted and transformed by 10 min of suckling. We found that a single injection of either neutralized acidic extracts of SME at a dose of one or two SME equivalents per rat or 625 ng dopamine effectively prevented both the depletion of PRL within the pituitary and the subsequent rise in plasma PRL when given 1-3 min before the onset of suckling. Likewise, a single injection of bromocriptine (0.5 mg) given 20-30 min before the onset of suckling totally blocked pituitary depletion and the subsequent release of PRL into the circulation. However, the PRL concentration rose normally in the plasma in response to suckling when either SME extract or bromocriptine was given after PRL depletion had first been effected by prior short term (10 min) suckling. These data indicate that the depletion-transformation phase but not the release phase (into the circulation) of PRL secretion is under inhibitory control by a dopaminergic PRL-inhibiting factor system.

Animals↗
PubMed1980

Evidence that thyrotropin-releasing hormone and a hypothalamic prolactin-releasing factor may function in the release of prolactin in the lactating rat.

We have compared the effectiveness of TRH and a rat hypothalamic PRL-releasing factor (PRF; previously incubated with rat serum to destroy TRH) in stimulating the release of PRL into the plasma of conscious lactating rats when injected before and after pituitary PRL had been depleted and transformed into releasable PRL by 10 min of suckling. TRH (1.25 microgramsss) and PRF [equivalent to 2.5 stalk median eminence (SME) fragments] each caused a small increase (38 and 30 ng, respectively) in the plasma PRL concentration within 10 min when injected into nondepleted mothers. The levels then fell quickly. Suckling, by comparison, caused a sustained 175 ng/ml increase above basal levels. Though PRL depletion occurred, as expected, as a result of suckling, there was no measurable depletion within the pituitaries of TRH- or PRF-injected rats. By contrast, the iv administration of TRH (doses ranging from 2-250 ng) and hypothalamic PRF (doses ranging from 0.2-1.0 SME equivalent) after depletion-transformation had been effected by 10 min of suckling resulted in a rapid and, in most instances, a sustained elevation in the plasma PRL concentration comparable to that seen after suckling. Dose-response relationships, though, were not clearly evident with either PRF or TRH. Neither saline, 1.25 microgram TRH previously incubated in serum, 50 mU oxytocin, 1 microgram dopamine, 25 microgram LHRH, nor an extract of cerebral cortex prepared in the same manner as hypothalamic TRH caused plasma PRL to rise after PRL depletion. We conclude that TRH and possibly a separate hypothalamic PRF have a stimulatory action upon the releasable, but not upon the depletion-transformation, phase of PRL secretion in the lactating rat.

Animals↗