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C J Phelps

Publications and source records attributed to C J Phelps.

At least 37 records · Page 2Linked to original sources
PubMed1994

Postnatal reduction in number of hypothalamic tuberoinfundibular dopaminergic neurons in prolactin-deficient dwarf mice.

Mice homozygous for the recessive 'Ames' dwarf mutation have undetectable serum or pituitary prolactin (PRL). Accompanying this pituitary deficiency is a marked reduction of dopamine (DA) and its rate-limiting synthetic enzyme tyrosine hydroxylase (TH) in PRL-regulating tuberoinfundibular hypothalamic neurons. In order to determine whether this deficit in adult Ames dwarf mice is congenital or arises postnatally, brains of dwarf (df/df) and normal (DF/?) littermate mice were assessed for TH immunoreactivity from 7 days through 2 months of age. Numbers of TH-positive neurons were counted in three hypothalamic DA areas: tuberoinfundibular A12, medial zona incerta A13, and anterior periventricular A14. There was an increase in the number of TH-positive neurons between 7 and 21 days of age in A12 and A14, but not in A13, for both DF/? and df/df mice. Between 21 days and 2 months of age, cell numbers were the same in all three areas in DF/? mice and in A13 and A14 in df/df mice. However, A12 TH-positive cell number in dwarfs decreased significantly (p < 0.01) between 21 days and 2 months, and was markedly lower (p < 0.001) in df/df than in DF/? mice at 2 months of age. The results emphasize the specificity of the dopaminergic neuron reduction in the Ames dwarf, which is restricted to the PRL-regulating tuberoinfundibular region. The data also indicate that the dwarf DA/TH deficit has an onset in late postnatal development, suggesting a response to absence of target PRL, rather than a primary hypothalamic effect of the dwarf mutation.

Animals↗
PubMed1994

Pituitary hormones as neurotrophic signals: anomalous hypophysiotrophic neuron differentiation in hypopituitary dwarf mice.

Anterior pituitary hormones are known to exert dynamic negative feedback effects on their respective regulatory ("hypophysiotropic") neurons in the hypothalamus. The purpose of this review is to present the evidence for a theory that the effect of pituitary hormones on these hypophysiotropic neurons is neurotrophic, extending beyond dynamic feedback to influence upon cell survival, phenotypic differentiation, and axonal connectivity. To that end, the adult condition and the development of hypophysiotropic neurons in mutant mice which lack pituitary growth hormone (GH) and prolactin (PRL) are presented as models of the effect of absent specific neurotrophic signals. The expression of the neurohormones which inhibit PRL and GH secretion, dopamine (DA) and somatostatin, respectively, is markedly reduced in the hypothalamus of the hypopituitary dwarf mouse, and this adult condition is the result of postnatal failure to develop or actual regression, which may include neuronal cell death. The deficit in DA may be reversed by PRL replacement, but only if initiated at an identified critical postnatal period. Conversely, expression of the stimulatory GH-releasing hormone (GHRH) is markedly increased in the dwarf mouse hypothalamus. The loss of DA and the increase in GHRH occur in the same hypothalamic area, suggesting neuronal phenotypic plasticity in response to absence of pituitary feedback signals. The axonal terminations of extant GH- and PRL-regulating neurons in external median eminence appear to be reduced, suggesting that pituitary signals are required for appropriate axonal guidance during development, even though an endocrine vascular route intervenes between these regulatory neurons and their target secretory cells. The collective observations indicate that GH and PRL may be regarded as neurotrophic factors for their respective regulatory neurons in the hypothalamus.

Animals↗
PubMed1993

Developmental assessment of hypothalamic tuberoinfundibular dopamine in prolactin-deficient dwarf mice.

Development of the hypophysiotropic hypothalamus in PRL-deficient Ames dwarf (df/df) mice was examined for steady state dopamine (DA) by visualization using formaldehyde-induced catecholamine histofluorescence and by quantification using catecholamine HPLC at selected postnatal ages (7, 14, 21, 30, and 90 days). Phenotypically normal (DF/?) littermate mice were compared with dwarfs by both methods at each age. The studies were designed to investigate whether the known deficiency in hypothalamic tuberoinfundibular DA in adult dwarfs is present neonatally or develops over the postnatal period. The anterior pituitary of each mouse was processed for GH and PRL immunocytochemistry. At 7 days of age, GH immunostaining was robust, and scattered PRL-positive cells were noted in DF/? pituitary. Homogeneously distributed PRL cells increased in number through 30 days of age in normal mice. Neither GH nor PRL immunoreactivity was present in df/df mice at any age. At 7, 14, and 21 days of age, hypothalamic DA tuberoinfundibular histofluorescence was comparable in df/df and DF/? mice. At 90 days of age, tuberoinfundibular histofluorescence in normal mice remained intense, but was virtually undetectable in dwarfs. The developmental change affected only tuberoinfundibular neurons, since DA histofluorescence in nonhypophysiotropic areas, such as substantia nigra (SN), was qualitatively comparable for df/df and DF/? for all ages examined. Norepinephrine (NE) fluorescence in hypothalamus was also comparable for df/df and DF/?. Catecholamine HPLC provided quantitative confirmation of histofluorescence observations. DA and NE levels in both hypothalamus and ventral midbrain, including SN, increased during development in both df/df and DF/? brains. NE levels were not different between dwarf and normal animals at any age in either medial basal hypothalamus (MBH) or SN. The DA concentration in SN was not different between df/df and DF/? at any age examined. MBH DA was comparable in df/df and DF/? mice at 7, 14, and 21 days of age; at 30 and 90 days, MBH DA was markedly lower (P < 0.001) in dwarf than in normal mice. Although MBH DA in dwarfs was comparable to that in normal mice at 21 days, the increase in dwarfs between 14 and 21 days was not statistically significant. Thus, the hypothalamic DA deficit that exists in adult dwarf mice is not present neonatally and represents a failure to increase DA compared with normal mice after 14 days of age. The failure of continued development of hypophysiotropic tuberoinfundibular DA neurons in dwarf mice is correlated chronologically with absent pituitary PRL production.

Animals↗
PubMed1993

Prolactin replacement during development prevents the dopaminergic deficit in hypothalamic arcuate nucleus in prolactin-deficient Ames dwarf mice.

PRL-deficient dwarf mice exhibit marked reduction in dopamine (DA) and in tyrosine hydroxylase (TH) immunoreactivity in the PRL-regulating neurons of the hypothalamic arcuate nucleus (catecholaminergic area A12). Recent studies in this laboratory have revealed that this condition develops postnatally, in that A12 DA fails to increase and the number of TH-positive cells decreases after 21 days of age. The present study was designed to test whether PRL replacement during the early postnatal period would increase DA and TH expression in dwarfs. Ames dwarf (df/df) and normal sibling (DF/?) mice were treated with daily injections of ovine PRL (50 micrograms, ip) or vehicle for 30 days starting on postnatal day 12. Brains were evaluated by catecholamine histofluorescence and TH immunocytochemistry at the end of the treatment period. TH-positive cells were counted in A12 and medial zona incerta (area A13) and also differentially within A12, in dorsal and ventral regions, and at anterior, middle, and posterior levels. Histofluorescence and TH-positive cell number (P < 0.01) in vehicle-treated dwarfs were greatly reduced compared with those in DF/? mice in A12, but not in A13. However, A12 fluorescence in PRL-treated dwarfs was comparable to that in DF/? mice. TH cell counts in A12 of PRL-treated dwarfs were significantly higher (P < 0.01) than those in vehicle-treated dwarfs and not different from those in either group of DF/? mice. Within A12, both dorsal and ventral TH cell numbers were reduced in vehicle-treated dwarfs (P < 0.01); the reduction was greater in the ventral subpopulation (P < 0.01). TH cell counts were lower in middle and posterior (P < 0.05), but not anterior, areas of A12 in vehicle-treated df/df mice compared with those in DF/? mice. TH cell numbers in all A12 regions in PRL-treated dwarfs were not different from those in DF/? mice. Thus, PRL replacement initiated before 2 weeks of age in dwarfs is effective in supporting DA and TH expression in both A12 neurons and median eminence external zone at normal levels, providing direct evidence that the DA/TH deficit in dwarfs is secondary to endogenous PRL deficiency.

Animals↗
PubMed1993

Growth hormone-releasing hormone peptide and mRNA are overexpressed in GH-deficient Ames dwarf mice.

Hypothalamic expression of growth hormone-releasing hormone (GHRH) was quantified morphologically in dwarf mice which exhibit spontaneous genetic GH absence. Mouse GHRH mRNA was assessed by in situ hybridization; densitometric evaluation of total mRNA in dwarfs showed levels 2.3-fold higher than in phenotypically normal siblings (p < 0.01); assessment of mRNA per neuron by autoradiographic grain counting indicated a 2.5-fold increase per cell in dwarfs (p < 0.005). GHRH peptide was evaluated immunocytochemically using a new mouse-specific antiserum; numbers of neurons containing detectable levels were 3-fold higher in dwarfs (p < 0.005). The increase in GHRH mRNA corroborates that reported previously in the GH-deficient little mouse, and after hypophysectomy in rats; GHRH peptide increase contrasts with previous reports of the effect of acute GH removal by hypophysectomy, in which GHRH levels fell. The results suggest that chronic GH deficiency is accompanied by increased translation as well as transcription of GHRH.

Animals↗
PubMed1992

Prolactin response to anesthetic stress and beta-endorphin is altered in female rats treated neonatally with monosodium glutamate.

MSG (4 mg/g, sc) or saline was administered to neonatal female rats on days 1, 3, 5, 7 and 9. Study 1) Prl levels were assessed at 30, 60 and 75 days after birth to monitor possible development of hyperprolactinemia. No hyperprolactinemia was observed at any time studied. Study 2) MSG and control rats were administered pentobarbital anesthesia at 2 months of age. At 20, 60 and 90 min following anesthesia, plasma was collected for assay of Prl. 20 min prior to the 90 min bleeding, BE (5 micrograms/5 ul) was stereotaxically administered, into the third ventricle. MSG-treated rats had an attenuated Prl response to the stress of anesthesia (bleeding 1). Prl levels in control and MSG-treated rats were similar at 60 min post-anesthesia (bleeding 2) which represented a return of Prl levels to baseline after stress-induced elevation of Prl. Control and MSG-treated rats exhibited an increase in plasma Prl following intracerebroventricular BE; however, the amplitude of this response was markedly attenuated in the MSG-treated animals (bleeding 3). Thus, an observed loss of TH-positive neurons in the arcuate nucleus of the hypothalamus following MSG treatment and the attenuated response of Prl to anesthesia-stress and BE administration suggests that Prl secretion in response to these agents is operative through inhibition of the TIDA system. Furthermore, these studies show that the Prl response to these agents (anesthetic and BE) is intact but sub-operational in MSG-treated rats.

Anesthesia↗
PubMed1992

Hypothalamic preprosomatostatin messenger ribonucleic acid expression in mice transgenic for excess or deficient endogenous growth hormone.

The influence of altered endogenous GH status on somatostatin (somatotropin release-inhibiting hormone; SRIF) gene expression was studied in two transgenic mouse models. Transgenic dwarf mice carried the rat GH gene promoter fused to the diphtheria toxin A-chain gene, placing toxin expression under GH promoter control. As a result, the toxic product of the transgene ablated all GH-expressing cells, resulting in undetectable circulating GH, reduced weight (10.6 +/- 1.0 g for transgenic dwarfs vs. 29.5 +/- 1.7 g for controls; P less than 0.001), and no detectable somatotrophs. Transgenic giant mice contained a construction combining a widely expressed metallothionein promoter and the human GH-releasing hormone (hGHRF) structural gene. Transgene expression of hGHRF resulted in overproduction of endogenous mouse GH in the anterior pituitary and weight increases (42.7 +/- 2.7 g for giants vs. 29.5 +/- 1.7 g for controls; P less than 0.005). Using in situ hybridization, control mice, transgenic dwarfs, and transgenic giants were compared for levels of prepro-SRIF mRNA. Hybridization signal intensities for prepro-SRIF mRNA were similar in transgenic dwarfs to those in littermate nontransgenic mice in non-GH-regulating regions of the brain, such as cortex (control, 31 +/- 2 U; dwarf, 27 +/- 2) and reticulothalamic nucleus (control, 41 +/- 2 U; dwarfs, 39 +/- 3). Transgenic giant mice had hybridization intensity of SRIF mRNA similar to that of normals in cortex (controls, 31 +/- 2 U; giant, 27 +/- 1) and reticulothalamic nucleus (controls, 41 +/- 2 U; giant, 40 +/- 4). In the GH-regulating neurons of the anterior periventricular hypothalamus (PeN), prepro-SRIF mRNA signal in transgenic dwarf mice decreased to 60% of that in controls (88 +/- 13 U for dwarfs vs. 147 +/- 17 U for controls; P less than 0.01), although the numbers of mRNA-expressing cells in the PeN were not different between the transgenic dwarfs and controls (dwarfs, 69 +/- 6 cells; controls, 72 +/- 4 cells). The transgenic giant mice had 230% higher prepro-SRIF mRNA signal than control mice in the PeN (343 +/- 30 U in giants vs. 147 +/- 17 U in controls; P less than 0.001). Again, the numbers of mRNA-expressing cells were not different in giants (57 +/- 9) and normals (72 +/- 4). These results suggest that while the lack of endogenous GH is accompanied by a slight decrease in transcriptional expression of SRIF in the PeN, the overproduction of endogenous GH greatly stimulates hypothalamic SRIF steady state mRNA levels.

Animals↗
PubMed1992

Quantification of vasoactive intestinal peptide immunoreactivity in the anterior pituitary glands of intact male and female, ovariectomized, and estradiol benzoate-treated rats.

There are considerable data suggesting that vasoactive intestinal peptide (VIP) is involved in the regulation of PRL secretion; however, the role and cell of origin of anterior pituitary VIP remain to be determined. Immunocytochemical (ICC) studies have generally failed to detect VIP-immunoreactive (IR) cells in the pituitary of the untreated rat, although VIP-IR cells have been observed in the pituitaries of hypothyroid or estrogen-treated rats. This study was designed to examine the cellular distribution and tissue content of VIP in the anterior pituitary gland of rats under selected endocrine conditions known to alter the rates of PRL and VIP synthesis and secretion. To this end, anterior pituitary VIP and PRL content (ICC and RIA) and serum PRL levels were determined in ovariectomized (OVX) and OVX rats 3 days after treatment with 7 or 70 micrograms estradiol benzoate (EB). For comparison, pituitary VIP and PRL content (ICC and RIA) and serum PRL levels in untreated male and diestrous female rats were determined. Immunostaining for VIP was accomplished using a newly developed primary antiserum. Significant numbers of VIP-IR cells per 5-microns section were found in the anterior pituitary glands of all animals examined (275 +/- 33 in diestrous to 481 +/- 103 cells in male rats). VIP was not colocalized with PRL in any of the pituitaries regardless of steroid treatment or sex. Furthermore, the number of VIP-IR cells per pituitary gland was not significantly correlated with sex or EB treatment. Treatment with 70 micrograms, but not 7 micrograms, EB significantly increased the pituitary content of VIP and serum PRL levels compared to those after ovariectomy. However, both EB treatments resulted in a significant increase in pituitary PRL content compared to that in untreated OVX rats. Pituitaries from male rats had several-fold more VIP and less PRL content than pituitaries from diestrous rats. These data show that 1) in contrast to previous ICC studies, VIP-IR cells are readily detected in the anterior pituitary of intact male and female and OVX as well as EB-treated rats; 2) VIP is localized to cells other than lactotrophs, regardless of the steroid background; and 3) marked changes in anterior pituitary VIP content are not accompanied by changes in VIP-IR cell number.

Animals↗
PubMed1991

Hypothalamic dopaminergic neurons in transgenic dwarf mice: histofluorescence, immunocytochemical, and in situ hybridization studies.

Spontaneous dwarf mice, in which both growth hormone (GH) and prolactin (PRL) are undetectable, are severely deficient in the PRL-inhibiting catecholamine dopamine (DA), as well as its synthetic enzyme, tyrosine hydroxylase (TH), in the basal hypothalamus (Phelps et al., Cell Tissue Res., 240:19-25, 1985; Phelps, Brain Res., 416:354-358, 1987). In contrast, transgenically constructed dwarf mice (Behringer et al., Genes Dev., 2:453-461, 1988) show complete ablation of pituitary GH cells, but PRL cells are retained at a level of approximately 10% of normal. In order to determine the feedback effect of this reduced, rather than absent, PRL on hypothalamic DA neurons, brains of transgenic dwarf mice were examined for catecholamine transmitters by histofluorescence, for the synthetic enzyme TH by immunocytochemistry, and for TH mRNA expression by in situ hybridization. DA histofluorescence in transgenic dwarfs was comparable to that of normal littermate mice in nonpituitary regulating areas (perikarya of zona incerta [A13] of hypothalamus and in midbrain substantia nigra area [A9]). Arcuate nucleus (A12) DA neurons that inhibit PRL secretion, however, showed dim to absent fluorescence in perikarya and in external median eminence terminals in dwarfs. There were reduced (P less than 0.05) numbers of A12 TH-immunoreactive neurons in transgenic dwarfs, to approximately 60% of those in normal mice. In contrast, TH-positive neurons in other hypothalamic areas (A13, A14) had average populations equivalent to those in normal mice. Quantification of TH mRNA abundance by in situ hybridization using both image analysis of hybridization over the arcuate nucleus, and grain counts per individual A12 cell in this nucleus, indicated that relative mRNA levels were the same in normal and transgenic dwarfs. The observations indicate that reduction in pituitary PRL is accompanied by defective expression in hypothalamic tuberoinfundibular neurons, which is severe at the DA neurotransmitter level, significant regarding observable TH immunoreactivity, and undetectable with regard to TH mRNA expression. Collectively, the findings suggest that posttranscriptional processes are involved with the mediation of PRL feedback upon hypothalamic neurons. Technically and quantitatively, the report presents the feasibility of simultaneous evaluation of transmitter histofluorescence, synthetic enzyme immunocytochemistry, and mRNA expression in individual animals.

Animals↗
PubMed1991

Construction and expression of the complete Clostridium difficile toxin A gene in Escherichia coli.

Cloned fragments constituting the 8.1-kb toxin A gene of Clostridium difficile were used to reconstruct the intact gene. The recombinant toxin expressed in Escherichia coli was cytotoxic, enterotoxic, and lethal. In addition, toxic lysate caused hemagglutination of rabbit erythrocytes. The toxic activities were inhibited by antibody specific for toxin A. Our findings demonstrate that the biological activities exhibited by native toxin A are functions of a single protein encoded by the 8.1-kb toxin A gene, independent of any other C. difficile gene products.

Animals↗
PubMed1990

Catecholamine reinnervation of supraoptic nucleus after deafferenting mechanical lesions and superior cervical ganglionectomy: histofluorescence and functional assessments in young adult and aged rats.

Catecholaminergic innervation of the hypothalamic vasopressin (VP)-secreting supraoptic nucleus (SON) was examined at selected intervals after deafferenting neurosurgical lesions, with respect to potential contribution of peripheral vascular sympathetic fibers. Young adult (3 months) and aged (20 months) male F344 rats were subjected to mechanical knife-cut lesion just caudal and medial to the SON, superior cervical ganglionectomy (SCGx), or both surgeries. SON and lesion sites were assessed at 4, 14, 30 or 45 days after surgery, by CA histofluorescence. Functional evaluation in rats subjected to chronic lesions consisted of monitoring water balance (water consumption and urine volumes, and urine osmolality and VP content) in individual rats for presurgical and postsurgical intervals. Histofluorescence evaluation showed that SCGx did not affect the overall SON fluorescence pattern, although a minor sympathetic contribution to that pattern was discerned by comparing SON in rats subjected to lesion alone vs SCGx + lesion. Morphological reinnervation of SON was accomplished at 30 days in young rats, and 45 days in aged rats, after both lesion and SCGx. In young rats, histofluorescence density 30 days after deafferentation was denser than the innervation pattern seen in intact (sham-lesioned) animals, while reinnervation at 45 days postsurgically in aged rats only approximated the presurgical pattern. Vasopressin excretion and corresponding water conservation measures were compromised by SON deafferentation at both ages; excreted VP levels and water balance did not rebound to presurgical values at chronic postsurgical intervals in either young or aged rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic Fibers↗
PubMed1990

Birthdates of the growth hormone releasing factor cells of the rat hypothalamus: an autoradiographic study of immunocytochemically identified neurons.

Growth hormone releasing factor (GRF) neurons in the arcuate nucleus of the hypothalamus and somatostatin (SRIF) neurons in the anterior periventricular region of the hypothalamus act to control the release of growth hormone from the anterior pituitary. To investigate the possibility that the growth-controlling functions of these cells might be compromised by injuries to the developing brain, it is important to know the details of the production and differentiation of these small, specialized cell groups. The overall pattern of cell production in the hypothalamus is known from autoradiographic studies with general nuclear stains, but no data are available on the birthdates (times of final mitoses) of GRF-producing cells. The present study was undertaken to determine when the GRF cells form. Counts of immunocytochemically identified GRF cells labeled on given days were taken from serial coronal sections through the hypothalamus of adult rats labeled on the 10th-17th days of gestation (day of finding a vaginal plug = day 1). As has been shown for the hypothalamus in general, the GRF cells showed a gradient of production from anterior to posterior. The peak of anterior cell proliferation was on day 13, middle cells on day 14, and posterior cells on day 15. These dates are 1 or 2 days earlier than those of GRF-negative cells in the same regions. No lateral to medial gradient of formation was seen in GRF cells. Rather, the laterally placed cells along the base of the brain and those surrounding the ventromedial nucleus formed simultaneously with the GRF cells of the arcuate nucleus. The birthdating results presented here are in agreement with the results of studies of teratogens which suggest that rat postnatal growth is reduced most severely by exposure to neurotoxic agents on days 12 or 13 of gestation. On the basis of data for the whole hypothalamus, such treatments would appear to be too early to interfere with cell production for the arcuate nucleus, but the timing fits the period of vulnerability as defined by the birthdates determined in the present study for the subpopulation of cells destined to produce GRF.

Animals↗
PubMed1990

Molecular characterization of the Clostridium difficile toxin A gene.

The gene encoding the toxin A protein of Clostridium difficile (strain VPI 10463) was cloned and sequenced. The coding region of 8,133 base pairs had a mol% G + C of 26.9 and encodes 2,710 amino acids. The deduced polypeptide has a molecular mass of ca. 308 kilodaltons. Nearly a third of the gene, at the 3' end, consists of 38 repeating sequences. The repeating units were grouped into two classes, I and II, on the basis of length and the low levels of DNA sequence similarities between them. There were seven class I repeating units, each containing 90 nucleotides, and 31 class II units, which, with two exceptions, were either 60 or 63 nucleotides in length. On the basis of DNA sequence similarities, the class II repeating units were further segregated into subclasses: 7 class IIA, 13 class IIB, 5 class IIC, and 6 class IID. The dipeptide tyrosine-phenylalanine was found in all 38 repeating units, and other amino acid sequences were unique to a specific class or subclass. This region of the protein has epitopes for the monoclonal antibody PCG-4 and includes the binding region for the Gal alpha 1-3Gal beta 1-4GlcNAc carbohydrate receptor. Located 1,350 base pairs upstream from the toxin A translation start site is the 3' end of the toxin B gene. Between the two toxin genes is a small open reading frame, which encodes a deduced polypeptide of ca. 16 or 19 kilodaltons. The role of this open reading frame is unknown.

Amino Acid Sequence↗
PubMed1988

Effects of bromocriptine on prolactin cellular hypertrophy, proliferation and secretory activity in diethylstilbestrol-induced pituitary tumors.

Pituitary tumors induced by chronic diethylstilbestrol (DES) treatment in female F344 rats were treated subsequently with bromocriptine (BC). Effects of BC on separable subpopulations of lactotrophs were examined. Enzymatically dissociated cells from individual pituitaries were assessed regarding total number, relative lactotroph population, intracellular prolactin (PRL) content, PRL release in primary culture, and density alterations by separation in Ficoll-Hypaque or after sedimentation at unit gravity. In addition to the treatment and analysis of in situ tumors, the effects of BC treatment in vitro were assessed, using tumor cells which were first separated on Ficoll-Hypaque. Cell proliferation was assessed by cell cycle analysis, using DNA measurement by laser flow cytometry. BC treatment of tumors reversed the effects of DES on pituitary weight, PRL content and in vitro PRL release. Total cell recovery was not affected by BC, but cell separation showed that BC reduced the number of larger PRL-containing cells. Cell cycle analysis showed a decrease in numbers of cells in S and G2 cycle phases after BC in only one of four experiments. BC had an effect on proliferation in only the upper gradient fractions, containing the smallest cells. Culture of Ficoll-separated tumor cells revealed greater PRL release among lighter/smaller cells. BC treatment inhibited PRL release from both light and dense cells. The results establish that PRL cell hypertrophy, as well as hyperplasia, results from DES treatment. Bromocriptine treatment reverses this hypertrophy concomitant with inhibiting PRL synthesis and release. Reversal of proliferation in tumor cells is not a major effect of bromocriptine treatment.

Animals↗
PubMed1988

Effects of zeranol on in vitro growth hormone release by lamb and rat pituitary cells.

A series of experiments was conducted to evaluate the effect of zeranol on release and synthesis of growth hormone (GH) by anterior pituitary cells established in either static or continuous flow cultures. Young adult male rats, slaughter-age lambs and juvenile lambs were used as sources of pituitary cells. In static primary cell cultures, no consistent effect of zeranol at 10(-7), 10(-9) or 10(-11) M was demonstrated by either rat or ovine cells. Rat pituitaries established in perifusion culture chambers showed no repeatable response to zeranol. Dissociated cells from lambs established in perifusion culture, however, had significant increases in release of GH in response to 37% of zeranol pulse exposures. When dissociated cells from juvenile lamb pituitaries were used, up to 10-fold increases in GH release consistently were measured within minutes of exposure to zeranol.

Animals↗
PubMed1987

Isolated deficiency of tyrosine hydroxylase immunoreactivity in tuberoinfundibular neurons in pituitary prolactin-deficient Snell dwarf mice.

Light microscopic morphology and relative numbers of tyrosine hydroxylase (TH)-immunoreactive neurons were assessed in hypothalamus of hypopituitary Snell dwarf mice, compared with normal mice of the same strain. Qualitatively, a specific deficit in staining of tuberoinfundibular neurons was noted in dwarf hypothalamus; TH-positive terminals were absent in dwarf median eminence, and morphology of axons in this region was aberrant. Qualitative observations were supported by quantitative assessment of hypothalamic dopaminergic neuron groups. Dorsal and intermediate TH-positive cells numbered 80% of those normal mouse brain; tuberoinfundibular (A12) TH-positive neurons in dwarf hypothalamus were 2% of those in normal mouse brain. The results imply that absence of pituitary hormone feedback impedes both structural and biochemical development of hypophysiotropic hypothalamic neurons.

Animals↗