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Biomedical subjects

M E Freeman

Publications and source records attributed to M E Freeman.

At least 73 records · Page 4Linked to original sources
PubMed1985

The proestrous surge of prolactin enhances sexual receptivity in the rat.

The influence of the proestrous surge of prolactin (Prl) on expression of feminine sexual behavior (lordosis) has been investigated. In the first experiment, proestrous rats were treated with a dopamine agonist, bromocriptine (CB-154; 100 micrograms at 1200, 1300, and 1600 h), which blocked the proestrous surge of Prl without affecting the preovulatory surge of luteinizing hormone. Such animals displayed depressed lordosis quotients (LQs) when compared to control animals at 2000 h on proestrus. However, in CB-154-treated animals given ovine Prl (10 I.U.) at 1400 h on proestrus, LQs were restored to control levels. Ovariectomized (OVX) rats primed with estradiol benzoate (EB; 2 micrograms for 2 days) produced surges of Prl that were similar in timing to those of proestrous. Once again, CB-154 treatment blocked this Prl surge and significantly depressed the LQ, whereas replacement with ovine Prl returned the LQ to control values. These results suggest that the Prl surge facilitates the expression of lordosis. Ovariectomized/adrenalectomized (ADX) and OVX/sham ADX rats were treated with EB (2 micrograms for 2 days) and tested for lordosis on Day 3. Adrenalectomized rats responded with lower levels of lordosis than did sham controls. Administration of progesterone (P4) to ADX rats on Day 3 enhanced the LQ compared to sham ADX values. CB-154 was ineffective in reversing the enhanced LQ, indicating that Prl may be acting through stimulation of adrenal progestins. These data taken together suggest that the proestrous surge of Prl contributes to the normal expression of feminine sexual behavior on proestrus.

Adrenalectomy↗
PubMed1985

The interaction of the medial preoptic area and the dorsomedial-ventromedial nuclei of the hypothalamus in the regulation of the mating-induced release of prolactin.

The medial preoptic area (MPOA) and the dorsomedial-ventromedial nuclei (DMN-VMN) of the hypothalamus regulate the mating-induced nocturnal and diurnal surges of prolactin in rats. The neural mechanisms governing the release of the two surges differ. For the nocturnal surge the MPOA serves an inhibitory role while the DMN-VMN serves a stimulatory role. The diurnal surge is controlled by both areas functioning as stimulatory centers. The goal of the present study was to explore the possibility of functional interactions between the MPOA and the DMN-VMN in control of mating-induced prolactin secretion. Stimulation of the MPOA in conscious, cervically stimulated (CS) females suppresses the nocturnal surge of prolactin. To determine if the inhibitory effects of the MPOA operate through the DMN-VMN, electrical stimulation was applied to the MPOA of conscious ovariectomized female rats bearing bilateral electrolytic lesions of the DMN-VMN. In the first experiment, control (sham-stimulated, sham-lesioned) CS females exhibited normal nocturnal surges which peaked at 03.00 h. MPOA stimulation (01.00-05.00 h) of both sham-lesioned and DMN-VMN lesioned CS females inhibited the release of their nocturnal surges. This suggests that the inhibitory function of the MPOA is independent of the DMN-VMN. MPOA stimulation can induce the release of a diurnal surge if the females are anesthetized with pentobarbital. In the second experiment, MPOA stimulation (15.00-19.00 h) of sham-lesioned anesthetized females produced elevated prolactin levels with significant peaks at 15.30 and 19.00 h. Anesthetized females with DMN-VMN lesions did not respond to MPOA stimulation with any change in prolactin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Detection of prolactin inhibitory activity in uterine epithelial cell secretions and rat serum.

We have shown that the uterus of the rat contains a substance that diminishes the release of the luteotropic hormone PRL by acting directly at the anterior pituitary gland. This study was designed to determine which cell type(s) within the uterus secretes this PRL inhibitory activity (PIA) and if PIA of uterine origin appears in circulation. Enzymatically dispersed cells from uteri of ovariectomized (OVX) rats were cultured for 24 h in serum-free Dulbecco's Modified Eagle's Medium. Estimation of PIA in the spent media from heterogeneous uterine cell cultures was evaluated after 24 h by the ability to suppress PRL release from confluent monolayers of cultured pituitary cells. Spent media from uterine cell cultures containing 0.125 X 10(6) or 0.25 X 10(6) cells/well failed to significantly suppress PRL secretion. However, media from 0.5 X 10(6) and 1 X 10(6) uterine cells/well induced 36% and 85% inhibition of PRL release, respectively, without affecting basal LH release. To determine which cell type(s) in the uterus is responsible for PIA secretion, whole uteri were partitioned into epithelial, stromal, and myometrial cell fractions by differential enzymatic dissociation. Varying numbers of cells from each fraction were cultured for 24 h. PIA in the spent media from the homogeneous uterine cell cultures was estimated by its ability to suppress PRL release from cultured anterior pituitary cells. Media from epithelial cell cultures suppressed PRL secretion in a dose-dependent fashion. Media obtained from cultures of a comparable number of stromal or myometrial cells had no significant effects on PRL secretion. LH secretion was unaffected by media obtained from any concentration of the various uterine cell types. Since cultured anterior pituitary cells treated directly with crude uterine extract for 24 h recover and secrete PRL at the same rate as untreated controls during a 72-h posttreatment interval, it is unlikely that the uterine PIA is either proteolytic or cytotoxic. To determine if PIA is detectable in peripheral circulation, sera obtained from OVX or OVX hysterectomized (OVX-HYST) donor rats were incubated with cultured anterior pituitary cells for 24 h. In response to the OVX sera, there was significant inhibition of PRL release. However, upon replacement of OVX sera with OVX-HYST sera, the inhibition was significantly reduced. Thus, PIA is higher in sera of rats bearing uteri. Taken together, these data suggest that the epithelial layer of the uterus secretes a PIA which probably reaches the hypothalamo-pituitary axis through the circulation.

Animals↗
PubMed1984

Uterus of the rat contains prolactin inhibitory activity.

Activity found in crude acid extracts of uterine tissue obtained from pseudopregnant, proestrous, or ovariectomized rats causes a dose-dependent inhibition of prolactin (PRL) release with a concurrent intracellular accumulation of PRL by anterior pituitary cells in culture. The absence of any significant effects imposed by the uterine extracts on basal luteinizing hormone or follicle-stimulating hormone secretion in these same cultures suggests that the activity is a noncytotoxic inhibitor of PRL secretion. Furthermore, failure of uterine extracts to degrade standard rat PRL after a 24-h coincubation at 37 degrees C suggests that the inhibitory activity is also nonproteolytic. That the activity is tissue specific is supported by the fact that extracts of gut, cardiac muscle, and diaphragm failed to block PRL release, whereas similarly prepared uterine extracts retained the ability to significantly depress PRL secretion. Haloperidol or bicuculline, dopaminergic and GABAergic receptor blockers, respectively, were ineffective in reversing the inhibitory effects of uterine extract on PRL secretion, suggesting that the inhibition is not due to dopamine or GABA. In addition to affecting basal release of PRL, in vitro larger doses of uterine extract were able to reverse the stimulatory effects of thyrotropin-releasing hormone on PRL secretion, indicating that the uterine-derived PRL inhibitory activity may also regulate stimulated PRL release. Taken together, these findings support the existence of a nondopaminergic, non-GABAergic inhibitory factor of uterine origin that specifically suppresses basal and stimulated secretion of PRL from cultured anterior pituitary cells.

Animals↗
PubMed1984

Hypothalamic regulation of mating-induced prolactin release. Effect of electrical stimulation of the medial preoptic area in conscious female rats.

Lesions of the medial preoptic area (MPOA) induce nocturnal prolactin surges similar to those initiated by cervical stimulation (CS). These same lesions can abolish diurnal prolactin surges previously initiated by CS. Based on these results the MPOA has been suggested to contain two functionally dissimilar sets of neurons, one inhibitory for the nocturnal surge and the other stimulatory for the diurnal surge. The present study sought to demonstrate the existence of these neural elements by electrically stimulating the MPOA of conscious ovariectomized female rats during those times of day when these neurons would be most active. Serial blood samples were collected via cannula before, during and after the stimulation. Stimulation of the MPOA (01.00-05.00 h) on day 2 after CS inhibited the nocturnal surge of prolactin while sham MPOA stimulation of CS females did not disturb the nocturnal surge. MPOA stimulation in non-CS females had no effect upon prolactin secretion. Application of MPOA stimulation (15.00-19.00 h) to CS females also suppressed the diurnal surge of prolactin. Sham-stimulated CS females, however, secreted a diurnal surge peaking at 17.00 h. Basal prolactin levels were unaffected by MPOA stimulation (15.00-19.00 h) in non-CS females. The results from these experiments suggest that the MPOA contains neurons inhibitory for both the nocturnal and diurnal prolactin surges. In a further attempt to show a stimulatory role for the MPOA in prolactin regulation, MPOA stimulation was applied (15.00-19.00 h) to pentobarbital anesthetized non-CS females. Pentobarbital treatment allowed the MPOA stimulation to trigger two prolactin peaks, one at 16.00 h and the other at 19.00 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Secretion of luteinizing hormone (LH) and pituitary receptors for LH-releasing hormone as modified by the proestrous surge of progesterone.

Pituitary glands of proestrous (PRO) rats display enhanced LH secretory response to LHRH when compared to pituitary glands of estrous (EST) rats. In addition proestrous pituitary glands display a self-potentiating (priming) response to LHRH, whereas estrous pituitary glands do not. This study addresses the role of the proestrous surge of progesterone in converting the proestrous-like LH secretory responses of the pituitary gland to those of estrus. Anterior pituitary glands were obtained from PRO and EST rats. In addition, Pro rats were treated with pentobarbital alone (PRO/PB) or with pentobarbital plus progesterone (PRO/PB-P4). Pentobarbital was given to prevent proestrous surges of LH and progesterone. Pentobarbital-treated animals were killed the day after treatment, estrus. Pituitary glands from each group were tested for LH secretory response in a superfusion chamber with exposure of two 15-min pulses of 10 nM LHRH separated by 90 min, or assayed for LHRH receptor content using iodinated D-Ala6-LHRH. Anterior pituitary glands from PRO rats secreted higher levels of LH than EST rats in response to an LHRH pulse. Only PRO anterior pituitary glands secreted priming responses to LHRH. Though anterior pituitary glands obtained from pentobarbital-treated rats showed LH responses of similar magnitude to anterior pituitary glands of PRO rats after initial LHRH challenge, they did not display priming responses. Progesterone replacement (PRO/PB-P4) led to depressed secretory responses when compared to PRO pituitary glands similar to EST rats. LHRH receptor concentrations in pituitary glands of EST rats was lower than those in pituitary glands of PRO rats. Depression of pituitary LHRH receptor concentration from proestrus to estrus was prevented by pentobarbital-treatment on proestrus. Estrus-like depression of receptor concentration was restored after progesterone treatment (PRO/PB-P4). These data suggest the LHRH receptor depression on estrus is a consequence of the secretion of progesterone on proestrus. Further, the declining magnitude of the in vitro LH-secretory response to LHRH follows a declining LHRH receptor concentration; however no correlation exists between receptor number and ability to prime.

Animals↗
PubMed1983

Turnover rates of amino acid neurotransmitters in regions of rat cerebellum.

The turnover rates of aspartate, gamma-aminobutyric acid (GABA), glutamate, glutamine, alanine, serine, and glycine were measured in five regions of rat cerebellum. Turnover rates of the putative neurotransmitters (aspartate, glutamate, and GABA) were 2-20-fold higher than those of alanine and serine, and generally consistent with the proposed neurotransmitter functions for these amino acids. However, glutamate turnover was high and similar in magnitude in the deep nuclei and granule layer, suggesting possible release, not only from parallel fibers, but from mossy fibers as well. The differential distribution of turnover rates for GABA supports its neuronal release by Purkinje, stellate, basket, and Golgi cells, whereas aspartate may be released by both climbing and mossy fibers. The distribution of glycine turnover rates is consistent with release from Golgi cells, whereas alanine may be released from granule cell parallel fibers. Turnover rates measured in two other motor areas, the striatum and motor cortex, indicated that utilization of these amino acid neurotransmitters is differentially distributed in brain motor regions. The data indicate that turnover rate measurements may be useful in identifying neurotransmitter function where content measurements alone are insufficient.

Amino Acids↗
PubMed1982

Amino acid neurotransmitter utilization in discrete rat brain regions is correlated with conditioned emotional response.

The content and utilization of amino acid neurotransmitters were evaluated in discrete brain areas of rats exposed to a conditioned emotional response (CER) procedure and in control groups which received either equivalent yoked shock history (shock only) or compound stimulus presentation (tone only). On test day, CER animals suppressed responding and exhibited anxious behavior after presentation of the CS, while shock only and tone only control groups, or CER animals which received an acute dose of diazepam prior to testing, did not suppress. Few changes were observed in the content of amino acids, suggesting that the behavioral manipulations were acting within normal physiological limits. On the other hand, numerous changes were observed in the utilization (turnover, metabolism) of the amino acid neurotransmitters. The effects of a history of shock presentation (shock only versus tone only) were persistent long after the conditioning sessions were terminated, and resulted in decreased turnover of the amino acids in many areas. CER conditioning-emotion (CER versus shock only) produced an increase in the turnover of aspartate and glutamate in many structures, while changes in GABA turnover were generally limited to decreases in limbic areas. If CER represents an animal model of anxiety, these observations may suggest roles for neurons which utilize amino acids in mediating or responding to emotional components of the paradigm.

Amino Acids↗
PubMed1982

Brain neurotransmitter turnover correlated with morphine-seeking behavior of rats.

Neurochemical substrates of intravenous opiate self-administration were investigated in rats using littermate controls for vehicle and passive morphine infusion. The rates of turnover of the putative neurotransmitters, dopamine, norepinephrine, serotonin, gamma-aminobutyric acid, aspartate and glutamate were concurrently measured in eleven brain regions of rats intravenously self-administering morphine and yoked-morphine or yoked-vehicle infused littermates. The passive infusion of morphine resulted in significant changes in the rates of turnover of the biogenic monoamine and amino acid neurotransmitters in six brain regions with the caudate nucleus-putamen-globus pallidus showing the most changes. The contingent infusion of morphine resulted in changes in utilization rates that were generally greater in both magnitude and number than the effects of the drug itself. Twenty-nine significant changes were observed in the self-administering group with most changes occurring in limbic structures. The neurotransmitter turnover rate changes resulting from contingent administration suggest that the drug administration environment is an important factor that should be considered in studies of interactions between drugs and neuronal systems.

Amino Acids↗
PubMed1982

The imprint provided by cervical stimulation for the initiation and maintenance of daily prolactin surges: modulation by the uterus and ovaries.

This study describes the influence of ovarian steroids and a putative PRL release inhibitory substance of uterine origin on the imprint provided by cervical stimulation (CS) for the maintenance of nocturnal and diurnal surges of PRL secretion. Toward the end of the pseudopregnancy (psp) resulting from a sterile mating or artificial stimulation of the uterine cervix, ovarian estradiol secretion is enhanced, and luteal progesterone (P) secretion wanes. This shifting ratio terminates the surges of PRL by day 13 of psp. Ovariectomy on day 8 of psp and simulation of this pattern of steroid secretion with sc Silastic implants also resulted in termination of surges by day 13. However, ovariectomy on days 2, 4, or 6, followed immediately by implantation of the inhibitory regimen of ovarian steroids, did not result in termination of the noctural surge by days 7, 9, or 11, respectively. The diurnal surge was absent in all cases. A third and fourth CS applied on days 7 and 8 of psp were not able to overcome the effects of the inhibitory steroid regimen begun on day 8. PRL surges induced in ovariectomized rats by one 30-sec CS persist for 6 days (suboptimal stimulation), while surges induced by two 30-sec CS persist for at least 10 days (optimal). However, implantation o P or hysterectomy permits suboptimally stimulated ovariectomized rats to secrete nocturnal surges through day 10. These data indicate that optimal CS programs the PRL-releasing apparatus to secrete surges for a preset interval, during which time the system remains unresponsive to physiological inhibitory and excitatory input. However, suboptimal CS can be reinforced by imposition of P or removal of PRL inhibitory activity of uterine origin.

Animals↗
PubMed1981

An ovarian role in prolonging and terminating the two surges of prolactin in pseudopregnant rats.

Daily nocturnal (N) and diurnal (D) surges of PRL are characteristic of a pseudopregnancy (psp) induced by cervical stimulation (CS). These semicircadian surges persist for 13-14 days, after which time they cease, and psp ends. The purpose of this study was to describe the involvement of the ovarian steroids in the maintenance and termination of the N and D surges of PRL. CS of long term ovariectomized (OVX) rats resulted in N and D surges of PRL lasting 14 days. By day 16 after CS, neither surge of PRL was present. The sc placement of Silastic implants containing large quantities of progesterone in long term OVX-CS rats sustained and enhanced the N surge of PRL until at least day 16. The D surge was also sustained until day 16, but its magnitude was normal. Estradiol alone was capable of maintaining the D but not the N surge for this same time interval. However, pharmacological quantities of estradiol restricted the magnitude of the N surge generated in the progesterone-implanted animal. Since neither surge of PRL was present by day 14 after CS in intact rats, but at least the nocturnal surge was still present at this time in long term or acutely OVX rats, this implies an active role of ovarian steroids in the termination of PRL surges at the end of psp. At the end of psp, luteal progesterone secretion declines and follicular estradiol secretion increases. Varying sizes of Silastic implants containing progesterone or estrogen were placed into psp animals after acute ovariectomy on day 9 to approximate this ovarian steroid secretory pattern of intact psp rats. Only when the decrease in progesterone was coupled with a modest increase in estrogen was there a total cessation of the two daily surges of PRL in OVX-CS rats. The data suggest that the PRL surges end in the intact psp rat due to the waning response to CS as well as the shifting steroid ratio represented by the fall in progesterone in the presence of a small amount of estrogen.

Animals↗
PubMed1981

The role of the dorsomedial-ventromedial area of the hypothalamus in the control of prolactin secretion induced by cervical stimulation.

Cervical stimulation (CS) initiates daily nocturnal (N) and diurnal (D) surges of PRL, which persist for at least 10 days, in intact and ovariectomized (OVX) rats. To affect pituitary PRL release, CS probably acts through several areas of the hypothalamus. PRL regulation by one hypothalamic area, the dorsomedial-ventromedial nuclei (DMN-VMN), was investigated in the present study. Electrical stimulation of the DMN-VMN of rats with intact ovaries produces both N and D PRL surges of the same magnitude, timing, and persistence as those initiated by CS. However, in long term OVX rats, stimulation of the DMN-VMN results in N surges which last only until day 6 and D surges present only through day 2. OVX rats receiving sc Silastic implants containing progesterone on the day after DMN-VMN stimulation had larger N surges, which persisted only as long as those secreted by long term OVX untreated rats. The D surge was unaffected. Rats OVX immediately after DMN-VMN stimulation secreted N surges through day 10, but D surges only through day 6. CS of long term OVX rats bearing lesions or sham lesions within the DMN-VMN results in N surges persisting through day 10. However, D surges could not be initiated by CS in rats bearing DMN-VMN lesions. These results suggest that the DMN-VMN is one area which responds to CS by initiating N and D surges of PRL. Excitation of this area is a requirement for the initiation of D, but not N, surges of PRL. However, continuation of the N surge probably involves the excitation of other areas within the central nervous system.

Animals↗
PubMed1981

Control of the corpus luteum: a model system for toxicology research.

The rodent corpus luteum is an ephemeral structure releasing progesterone for only a few hours rather than several days. However, in response to the mating stimulus, sufficient prolactin is released from the pituitary gland in a unique pattern to activate the corpus luteum and maintain it in a secretory state for several days. Progesterone, secreted from the corpus luteum, prolongs the secretion of prolactin, while the uterus may secrete a substance which terminates the functional life of the corpus luteum directly and also acts upon he prolactin secretory apparatus within the hypothalamopituitary axis to terminate prolactin secretion.

Animals↗
PubMed1981

Gastrointestinal structure and function in Fabry's disease.

We evaluated gastrointestinal structure and function in 13 hemizygous males and 17 heterozygous females, five to 67 years old, from four kindreds with Fabry's disease. Gastrointestinal symptoms, noted in 62% (8/13) of the males and 29% (5/17) of the females, were present prior to the diagnosis of Fabry's disease in five patients; were discovered at the time of study in six patients and were associated with multiple other symptoms in two patients. Serum protein, albumin, folate, Vitamin B12, calcium, phosphorous, cholesterol and iron were normal in all 30 patients. Xylose absorption was normal in 2/2 males and 13/13 females studied. HLA B8 antigen was present in none of the males and 2/17 females. Peroral duodenal (one male), jejunal (six males, two females) and rectal (one male) biopsies on light microscopy demonstrated a normal villous pattern and luxol-fast blue positive "foamy" cell deposits in all males, while no deposits were visualized in the females. In all males and females studied, electron microscopic examination showed electron dense, intralysosomal "zebra-like" (0.5-0.75 micrometer.) bodies in the vascular endothelial and perithelial cells and in the cytoplasm of the small unmyelinated neurons, and perineurial cells. Despite the frequency of gastrointestinal symptoms, both malabsorption and celiac disease were absent.

Adolescent↗