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Large MtTW15 pituitary tumors produced 200- to 800-fold elevations in serum growth hormone (GH) and prolactin (PRL) levels. Female tumor hosts showed doubling in body weight, milk secretion, and a 2-fold hepatosplenomegaly. Pituitaries of host animals were reduced by about 50% in both weight and concentrations of GH and PRL. Large tumors were well-encapsulated, multinodular and showed variable amounts of necrosis and hemorrhage. Cytofluorometric analysis revealed a range of 100-fold in nuclear DNA content of tumor parenchymal cells which were chromophobic, pleomorphic and frequently mitotic. Concentrations of hormones in tumors were less than in normal pituitaries and highly variable with the ratio of GH/PRL ranging up to 30-fold within the same tumor. Immunostaining and linear scanning quantitation showed that about 50% of the tumor cells contained immunodetectable hormones. Comparison of immunostained adjacent sections showed that hormone-containing tumor cells were pleomorphic, unequally distributed within nodules, lacking in distinctive identifying morphological characteristics and that they contained GH or PRL but not both hormones simultaneously. Collectively our results show that large MtTW15 tumors are comprised of a markedly heterogeneous population of tumor cells and they suggest that the hormone-containing cells are monohormonal secreting tumor cells which can produce GH or PRL but not both hormones.
Anat Rec 1978 Mar
PMID:Heterogeneity of the MtTW15 mammosomatotropic tumor. I. Light microscopic evaluation of cell types by means of immunocytochemistry, morphometric quantitation, fluorescence cytophotometry and radioimmunoassay. 34 70

Two-day-old female rats were injected with 5 nmole/kg of 6,7-3H-11 beta-methoxy-17-ethylestradiol (R 2858 = moxestrol) and killed one hour later. The animals were decapitated and, the pituitary glands were removed, mounted on tissue holders and frozen in liquified propane. The tissue was then processed for autoradiography according to the thaw-mount technique. At the end of the exposure time, prior to photographic development, some of the tissue was fixed in 10% formalin and then photographically developed for autoradiography. The fixed tissue was subsequently stained immunocytochemically using antibodies to luteinizing hormone or prolactin. Between 10 and 15% of the cells of the pars distalis concentrated the synthetic estrogen or its metabolite. The immunocytochemical procedure revealed that both LH-gonadotrophs and lactotrophs concentrated the steroid. These studies along with earlier studies suggest that the neonatal rat pituitary contains only a small portion of the adult complement of estrogen receptors and that these receptors are dispersed across a number of cell types.
Anat Rec 1979 Aug
PMID:An autoradiographic and immunocytochemical study of the neonatal rat pituitary gland. 47 13

Prolactin is known to enhance the uptake and metabolism of testosterone in male accessory sex organs and to increase the weight of accessory sex organs from castrated rats over those from controls treated with testosterone alone. The present study was directed toward defining fine structural changes detectable with scanning and transmission electron microscopy which might accompany such responses. Accordingly, rat ventral prostate gland was examined from castrated animals which had received testosterone propionate and ovine prolactin singly or together, or which had received vehicle only. Unoperated animals served as additional controls. Post-castration glandular atrophy was not influenced by prolactin treatment alone. Testosterone restored epithelial height, secretory product, Golgi complexes and rough endoplasmic reticulum, such that cellular and tissue morphology was generally indistinguishable from that of unoperated controls. Prostatic tissue from animals given testosterone and prolactin simultaneously exhibited pleomorphic, cytoplasmic apical projections which extended into the acinar lumen. Transmission electron microscopy demonstrated that these blebs were devoid of organelles and microvilli; scanning electron microscopy revealed that the blebs were highly wrinkled and more numerous than were the projections observed in tissue from animals treated with testosterone alone, or in tissue from unoperated controls. It is suggested that such blebbing may reflect enhanced apocrine secretion in prolactin/testosterone stimulated restoration of the prostate gland in castrated rats.
Anat Rec 1978 May
PMID:Synergistic effects of prolactin and testosterone in the restoration of rat prostatic epithelium following castration. 64 36

The immune expulsion of gastrointestinal nematodes is impaired during lactation by the inhibition of the lymphocyte mediated component. As a result the population of worms may increase. At the same time, the fecundity of female worms in previously immune hosts may increase to approach that of worms in fully susceptible animals. There is good evidence that these events are primarily endocrinal in origin but although prolactin is probably involved, certain anomalies exist. These may reflect differences in the secretion pattern of the hormone in different phases of reproduction or they may indicate an interrelationship with a second hormone, for instance, adrenal glucocorticoids.
Vet Rec 1976 Dec 11
PMID:Effect of lactation on the immune response to gastrointestinal nematodes. 103 96

The recovery of rat prolactin cells following cessation of estrogen treatment is described. The ultrastructural changes induced by estrogen treatment in prolactin cells were observed and the recovery of these stimulated cells were followed for periods ranging from 20 hours to 15 days posttreatment. Treatment for 1 month caused some regression of somatotrophs in female rats, but induced an increase in the number of prolactin cells and caused these cells to hypertrophy. The stimulated prolactin cells showed extensive development of the granular endoplasmic reticulum which was often arranged in concentric whorls (Nebenkern) and most cells contained some small mature granules. 5-10 days after suspension of treatment many prolactin cells contained numerous secretory granules ranging in size from 150 to 500 mm. Only the largest (750 mm) exhibited the irregular shape characteristic of mature granules in normal prolactin cells. 15 days posttreatment most prolactin cells exhibited numerous secondary lysosomes and the mature secretory granules were similar in morphology to those of normal prolactin cells. Since the somatotrophs appeared not to be stimulated by the treatment it is difficult to accept the concept that somatotrophs can undergo transformation into prolactin cells.
Anat Rec 1976 May
PMID:Recovery of rat prolactin cells following cessation of estrogen treatment. 126 96

Immature 27-day-old female Sprague-Dawley rats were administered daily subcutaneous injections of dehydroepiandrosterone (DHEA, 5 mg/100 g BW) to induce the formation of ovarian follicular cysts. Groups of rats were killed on days 0, 10, 15, 20, 25, and 30. Ovaries from each group of rats were processed for light and electron microscopy and for follicular or cystic fluid hormone analysis. Normal antral follicle fluid, PMSG-treated preovulatory follicular fluid, and cystic fluids were analyzed for progesterone (P), estrone (E1), estradiol (E2), testosterone (T), delta 4-androstenedione (delta 4-A), 5 alpha-dihydrotestosterone (DHT), luteinizing hormone (LH), follicle stimulating hormone (FSH), and prolactin (PRL). DHEA induced anovulation, acyclicity, and the formation of follicular cysts. In certain antral follicles, there was a dramatic increase in the quantities of smooth endoplasmic reticulum (SER) in the granulosa cells and many mitochondria had tubular cristae. Further depletion of granulosa cell number was associated with intense blebbing of the cytoplasm into the follicle antrum. Formation of the ovarian follicular cyst was completed when the entire cyst was lined by a single layer of transformed granulosa cells in contact via adhering, gap, and tight junctions. These cells had little cytoplasm, mitochondria with lamellar cristae, vast basal and apical bands of microfilaments, and an extensive array of smooth-surfaced endocytotic invaginations on the basal plasma membrane. These endocytotic pits may subsequently form smooth-surfaced vesicles and thereby serve as one mechanism for moving fluid from the ovarian interstitium into the cyst. Theca interna cells were rarely observed in the peripheral regions of the cyst. Abundant smooth muscle cells were located beneath the basement membrane of the epithelial cells comprising the cyst wall. These acquired morphological and physiological features may ensure persistence of the ovarian cyst and thus potentiate a chronic pathological condition. In this study it was also shown that progesterone, estrone, and estradiol as well as androgen concentration increased in the follicle after PMSG treatment. With DHEA treatment, the follicular cystic fluid concentrations of these steroids progressively increased to extremely high levels concurrent with the development of the follicular cysts.(ABSTRACT TRUNCATED AT 400 WORDS)
Anat Rec 1992 Nov
PMID:Cystogenesis of the ovarian antral follicle of the rat: ultrastructural changes and hormonal profile following the administration of dehydroepiandrosterone. 144 64

The mode of secretory granule formation in prolactin cells was analyzed in thin or thick sections of pituitary glands from non-lactating or lactating female as well as from male rats. In all these animals, the Golgi apparatus of prolacting cells consists of a continuous twisted ribbon-like structure that branches and anastomoses to form a hollow sphere located in the juxtanuclear area. The early signs of secretory granule formation are observed along the trans-aspect of the Golgi ribbon where progranules appear as focal distensions simultaneously occurring anywhere in the last trans thiamine pyrophosphatase (TPPase)-containing Golgi element. In the transmost Golgi saccule, such dilatations usually contain several nodular masses of electron opaque material which are separated from each other and from the saccular membrane by a less intensely stained material. While this transmost saccule becomes more fenestrated, its focal polynodular distensions seemingly yield polynodular tubular progranules which are initially closely apposed and usually parallel to the trans face of the Golgi ribbon. Subsequently, these progranules, which frequently show small membranous tubules or tubular networks attached to them, are seen some distance from the Golgi stacks and progressively transform into the more compact polymorphous granules characteristic of prolactin cells. These observations suggest that the polynodular tubular progranules arise by fragmentation of portions of the trans-Golgi elements rather than by fusion of small uninodular granules budding from the edges of a trans-Golgi saccule. Once the progranules have been liberated, the rest of the transmost Golgi element appears to break down into small residual networks, tubules, and vesicles. Thus, in prolactin cells as in other glandular cells, the whole transmost Golgi element would fragment during formation of prosecretory granules.
Anat Rec 1992 Feb
PMID:Formation of secretory granules in the Golgi apparatus of prolactin cells in the rat pituitary gland: a stereoscopic study. 154 96

Cell-to-cell communication by gap junctions was investigated in the female rat anterior pituitary gland from 9 through 21 days of pregnancy and subsequently on days 2 and 20 of the lactational period. Compared with intact estrus females, the major morphological characteristics of the pituitary gland during pregnancy were remarkably developed prolactin cells and gonadotrophs. A close relationship of both cell types was clearly evident. Gap junctions were present at each of the time intervals studied; however, they were noted only between adjacent folliculo-stellate cells. No remarkable changes were noted in the number of gap junctions during the middle stage of pregnancy (day 9 through day 15), with the relative number resembling that found in intact, 90-day-old controls during estrus (0.47 +/- .01 junctions/follicle-control vs. 0.50 +/- 0.08--day 15 of pregnancy). In the later stages of pregnancy (day 17 through day 21), a demonstrable increase was observed (0.64 +/- 0.10--day 17, 0.79 +/- 0.11--day 19 and 0.72 +/- 0.12--day 21), whereas during the lactation, this pattern returned to that seen at midpregnancy. Since both prolactin and the gonadal steroid hormones dramatically fluctuate during pregnancy and lactation, it is postulated that they may have an active role in gap junction formation during these two phases of reproductive life.
Anat Rec 1992 May
PMID:Intercellular communication within the rat anterior pituitary gland: IV. Changes in cell-to-cell communications during pregnancy. 160 82

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.
Anat Rec 1991 Dec
PMID:Hypothalamic dopaminergic neurons in transgenic dwarf mice: histofluorescence, immunocytochemical, and in situ hybridization studies. 168 35

The present study examined the acute effects of 2 Br-alpha-ergocryptine (CB-154, a dopamine agonist) on mammotroph organelles during prolactin (PRL) suppression. Ovariectomized estrogen-primed rats received a single injection (sc) of 0.5 mg CB-154 and the animals were killed at intervals following injection. The anterior pituitary glands were fixed for electron microscopy and immunocytochemistry was used to confirm mammotroph identification. Serum PRL levels were determined by RIA. Following CB-154 administration, serum PRL was significantly (P less than 0.05) reduced within 15 minutes and was suppressed (P less than 0.01) to ovariectomized levels at 2 and 6 hours. A stereological analysis of mammotrophs in the central regions of the anterior pituitary showed that the Golgi complex volume was significantly (P less than 0.05) reduced at 2 hours after CB-154 treatment. However, the Golgi complex volume had recovered by 6 hours post CB-154 injection. In addition, the volumes of the mammotroph cells, the mature secretory granules, and the secondary lysosomes had significantly increased by 6 hours. There were no significant changes in any of the organelles following CB-154 in the mammotrophs from the peripheral regions of the gland. These studies show that the Golgi complex is especially susceptible to acute morphological changes induced by bromocryptine and that the mammotrophs in the central regions are more responsive to CB-154 than those in the peripheral regions.
Anat Rec 1991 Nov
PMID:Alteration of the mammotroph Golgi complex by the dopamine agonist 2 Br-alpha-ergocryptine (CB-154) in ovariectomized estrogen primed rats. 176 15


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