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Showing papers on "Prolactin published in 1984"


Journal Article
TL;DR: The results demonstrate a multihormonal control of normal prostate epithelial cell maintenance and proliferation without the direct participation of androgen.
Abstract: Selective nutritive conditions were used to isolate normal epithelial cells from fibroblasts in primary cell cultures prepared from adult rat prostate. The pure population of normal epithelial cells proliferated at an exponential rate on a simple polystyrene substratum with doubling times of 35 to 50 hr for 10 to 12 days in the absence of high epithelial cell density, other cell types, or added extracellular matrix elements. Optimization of the nutritive environment allowed direct analysis of the hormone:growth factor requirements for sustained proliferation of the isolated epithelial cells in serum-free medium. An in situ videometric method was used to assay the effect of over 30 known hormones and growth factors on proliferation of the prostate epithelial cell population. The results revealed direct mitogenic effects of insulin, epidermal growth factor, glucocorticoid, cholera toxin, one or more unidentified factors from bovine pituitary, and possibly prolactin. No direct mitogenic effect of androgen on isolated prostate epithelial cells could be demonstrated. Radioimmunoassay of androgen in the primary cultures showed that endogenous androgen was about 34 pM on Day 1 of culture and thus probably too low to mask a response to exogenous androgen. Deletion of any single active growth factor did not reveal an androgen response. The results demonstrate a multihormonal control of normal prostate epithelial cell maintenance and proliferation without the direct participation of androgen.

324 citations


Journal ArticleDOI
TL;DR: There was a marked blunting of the maximal prolactin response to the tryptophan in both the male and female patients, providing strong support for a possible serotonergic abnormality in depression.
Abstract: • There is considerable evidence that serotonergic function may be reduced in the brains of depressed patients. Serotonin is an effective stimulant of prolactin release, and intravenous (IV) tryptophan (the amino acid precursor of serotonin), when administered to healthy subjects, produces a reliable and robust increase in serum prolactin level. To evaluate serotonergic function in depressed patients, we gave 25 patients and 19 age- and sex-matched controls tryptophan, 7 g IV. There was a marked blunting of the maximal prolactin response to the tryptophan in both the male and female patients. The patient control differences could not be accounted for on the basis of age, sex, or time without medications. The data provide strong support for a possible serotonergic abnormality in depression.

276 citations


Journal ArticleDOI
27 Jul 1984-JAMA
TL;DR: The mean levels of total and nonspecifically bound testosterone as well as prolactin were significantly lower than in controls, although levels remained within the physiological range.
Abstract: To investigate whether endurance running in men produced basal hormonal changes similar to those reported in women, we obtained blood samples from 31 men running at least 64 km each week and 18 sedentary controls for measurement of levels of total testosterone, non-sex hormone-binding globulin-bound and free testosterone, luteinizing hormone, follicle-stimulating hormone, prolactin, and cortisol. The mean levels of total and nonspecifically bound testosterone as well as prolactin were significantly lower than in controls, although levels remained within the physiological range. Other hormone levels were similar in both groups. The lowered testosterone and prolactin levels parallel the changes reported in women runners. (JAMA1984;252:514-516)

259 citations


Journal ArticleDOI
TL;DR: The results suggest that the central serotonergic system is less responsive in depressed patients than controls, and fenfluramine, a serotonin releasing agent, was administered to 18 depressed patients and 10 controls.

243 citations


Journal ArticleDOI
01 Apr 1984-Cell
TL;DR: Test of the hypothesis that differences in the secretory rhythm of GH are responsible for sex-dependent liver functions of mice suggest that induction of MUP mRNA requires pulsatile occupancy of GH receptors, which is achieved naturally in males or by injection of GH, whereas chronic occupancy ofGH receptors is inhibitory.

223 citations


Journal ArticleDOI
TL;DR: Withdrawal of bromocriptine therapy is associated in most patients with reversal of its beneficial effects--return of hyperprolactinemia, return of excess growth hormone secretion, and exacerbation of Parkinson's disease.
Abstract: Bromocriptine, a specific dopamine receptor agonist, has been used for the treatment of various hyperprolactinemic conditions and as adjunctive therapy for acromegaly (with or without concomitant hyperprolactinemia) and Parkinson's disease. Bromocriptine is extremely effective in suppressing prolactin secretion regardless of the cause, in restoring gonadal function and fertility, and in decreasing the size of prolactin-secreting pituitary tumors. Most patients with acromegaly have clinical improvement with this drug. When bromocriptine is added to a regimen of levodopa or carbidopa, patients with Parkinson's disease frequently have additional clinical improvement and, in most patients, the levodopa or carbidopa dose can be reduced. Withdrawal of bromocriptine therapy is associated in most patients with reversal of its beneficial effects--return of hyperprolactinemia, return of excess growth hormone secretion, and exacerbation of Parkinson's disease.

217 citations


Journal Article
TL;DR: It is concluded that, to have an impressive antitumor effect, presence of the pineal gland is essential, and the probable site of melatonin action appears to be at both the Pineal gland and the hypothalamus.
Abstract: Exposure of female Holtzman rats to constant light (24 hr/day) immediately after birth significantly increased 9,10-dimethyl-1,2-benzanthracene-induced mammary cancer. Such “functionally pinealectomized” animals also revealed significant increase in the circulating level of prolactin and exaggerated development and proliferative activity of mammary epithelium, as measured by quantitation of terminal end buds and alveolar buds from the whole mounts and by DNA synthesis, respectively. Administration of melatonin (500 µg/day/rat i.p. given from 52 to 145 days of age) completely abolished the effect of functional pinealectomy by sharply reducing 9,10-dimethyl-1,2-benzanthracene-induced cancer incidence from 95% to 25% during the post-9,10-dimethyl-1,2-benzanthracene observation period which lasted up to 180 days. On the other hand, administration of melatonin to surgically pinealectomized animals exposed to constant light reversed the effect only partially by reducing the cancer incidence from 83% to 53%. Further, melatonin treatment in intact and surgically pinealectomized animals exposed to a short photoperiod revealed qualitatively similar differences in suppression of the cancer incidence. From these results, it is concluded that, to have an impressive antitumor effect, presence of the pineal gland is essential, and the probable site of melatonin action appears to be at both the pineal gland and the hypothalamus.

167 citations


Journal ArticleDOI
TL;DR: It is suggested that an increase in endogenous prolactin levels may be necessary for the development and maintenance of the summer pelage.
Abstract: This study investigated whether photoperiod-induced changes in circulating prolactin levels, which have been observed in the Djungarian hamster ( Yellon and Goldman, '83; Duncan and Goldman, ' 83a ), might be involved in seasonal pelage color changes in this species. Injection of ovine prolactin (100 micrograms/day) inhibited the short photoperiod-induced winter molt. This finding indicated that the suppression of endogenous prolactin levels normally occurring in short photoperiod-housed hamsters (Duncan and Goldman, ' 83a ) may induce the winter molt. Suppression of prolactin secretion with bromoergocryptine (200 micrograms/day) strongly inhibited the spring molt, while concomitant treatment with ovine prolactin (100 micrograms/day) overcame this effect of bromoergocryptine. Injection of bromoergocryptine (200 micrograms/day) stimulated the winter molt in castrated hamsters housed in long photoperiod; concomitant injection of prolactin (100 micrograms/day) reversed this effect as well. These findings strongly suggested that an increase in endogenous prolactin levels may be necessary for the development and maintenance of the summer pelage.

162 citations


Journal ArticleDOI
TL;DR: Results from this study suggest a neuroendocrine dysregulation in cluster headache in the endogenous clock which controls the pineal rhythmicity.
Abstract: The temporal organization of plasma melatonin. cortisol. growth hormone (GH) and prolactin secretion was examined in healthy rested controls and in patients suffering from episodic cluster headache. Eleven patients with typical cluster headache (10 men, 1 female) and 8 male controls were studied over a 24–h period: blood was collected at 2–h intervals during the day and at l-h intervals at night. Plasma melatonin. cortisol, GH and prolactin levels were determined by radioimmunoassay. Most of the cluster headache patients showed a decrease in nocturnal melatonin secretion and the melatonin rhythm was even completely abolished in one patient. Chronobiological analysis of the cluster headache patients' 24–h plasma melatonin profile showed a significant decrease in amplitude and mesor: these were 58.7 pg/ml and 34.4 pg/ml respectively in control subjects, versus 18.7 pg/ml and 17.6 pg/ml for the patients. In addition. patients showed a significant phase-advance in their melatonin rhythm For cortisol, the rhyt...

161 citations


Journal ArticleDOI
TL;DR: The growth-related protein identified by hybridization to cloned cDNAs appears to be a new member of the prolactin-growth hormone family and has been called "proliferin."
Abstract: As part of the proliferative response to serum, mouse 3T3 cells produce a set of growth-related mRNAs identified by hybridization to cloned cDNAs. One of these mRNAs, which is about 1 kilobase long, appears within a few hours after stimulation of resting cells with serum or platelet-derived growth factor and reaches a high level during the transition from the G1 to the S phase of growth. This mRNA is translated in vitro into a protein of approximately 25 kilodaltons. The corresponding cloned cDNA of 791 base pairs has been sequenced; it contains a single open reading frame that encodes a protein of 224 amino acids with extensive sequence homology to mammalian prolactins. The initial 29-amino acid segment of the encoded protein resembles the signal sequences of prehormones. That the growth-related protein is not mouse prolactin is indicated by comparison of its predicted amino acid composition with that of mouse prolactin and by the distinct fragment patterns seen when restricted mouse DNA is probed with the cloned cDNA or rat prolactin cDNA. Therefore, the growth-related protein appears to be a new member of the prolactin-growth hormone family. Because of its relationship to prolactin and growth hormone and its association with cell proliferation, the protein has been called "proliferin."

155 citations


Journal ArticleDOI
TL;DR: It is suggested that the lymphocyte prolactin receptor may be involved in regulating lymphocyte function, and that one of the actions of cyclosporine is to block this rather ubiquitously occurring receptor.

Journal ArticleDOI
TL;DR: Results show that E2-induced tumorigenesis of the AP is associated with the development of a direct arterial blood supply and that this arteriogenesis is closely correlated with the sensitivity of two strains of rats to the tumorigenic action of E2.
Abstract: The rat anterior pituitary gland (AP) receives all of its blood supply via the hypophyseal portal circulation. We now report, in rats with estradiol (E2)-induced prolactin-secreting tumors, that newly formed arteries directly supply the AP and that this arteriogenesis is closely correlated with the sensitivity of two strains of rats to the tumorigenic action of E2. Fischer 344 rats, a strain extremely sensitive to E2, and Sprague-Dawley rats, a less sensitive strain, were ovariectomized and implanted with E2-filled or empty Silastic capsules. Ten to 63 days later, microspheres (15 microns) were injected into the heart. Normally microspheres do not reach the AP because they are trapped in the primary portal capillary plexus. Some animals were also perfused with vascular cast material. In Fischer rats, after 63 days of E2, the pituitary weight, serum prolactin, and number of microspheres in the AP were 5-, 42-, and 18-fold greater than control values, respectively. The same parameters in E2-treated Sprague-Dawley rats were 2-, 27-, and 7-fold greater than control values. Vascular casts from E2-treated Fischer rats revealed numerous arteries entering the AP. No arteries to the AP were observed in Sprague-Dawley controls. These results show that E2-induced tumorigenesis of the AP is associated with the development of a direct arterial blood supply. We hypothesize that the regions supplied by these new arteries would receive systemic blood containing subphysiological concentrations of dopamine. The loss of dopaminergic inhibition in concert with E2 stimulation may lead to tumor formation.

Journal ArticleDOI
TL;DR: Endocrine changes at parturition result in dramatic changes in receptor populations of key tissues such as adipose and mammary tissues, and relationship between hormone receptors and specific cellular metabolic pathways remains unresolved.
Abstract: Lactogenesis signals the shift from uterine nutrient transfer to the fetus to neonatal nourishment at the mammary gland. Metabolic adaptations involved in this process are under endocrine regulation. Key events include an increase in blood flow to mammary tissue, a decrease in nutrient utilization by peripheral tissues and an increase in nutrient utilization by mammary tissue for milk synthesis. Deficits of certain substrates during early lactation require mobilization of those substrates from depot stores. Changes in metabolism of various tissues are related to changes in hormone receptor populations of those tissues and hormone concentrations in blood. Hormone receptors are therefore the primary mechanism by which information from the endocrine systems is linked to cellular metabolism. Endocrine changes at parturition result in dramatic changes in receptor populations of key tissues such as adipose and mammary tissues. Knowledge in this area, however, is incomplete. Relationship between hormone receptors and specific cellular metabolic pathways remains unresolved.

Journal ArticleDOI
TL;DR: These studies assessed the effects of age on the ability of estradiol-17 beta (E2) to induce LH and PRL surges in ovariectomized young and middle-aged rats that previously had normal estrous cycles.
Abstract: These studies assessed the effects of age on the ability of estradiol-17β (E2) to induce LH and PRL surges in ovariectomized young and middle-aged rats that previously had normal estrous cycles. We determined whether any changes in the timing or amplitude of these surges could be correlated with changes in pituitary responsiveness to GnRH or with changes in norepinephrine (NE) and dopamine (DA) turnover rates in microdissected brain regions involved in cyclic gonadotropin release. Young (3–4 months old) and middle-aged (9–12 months old) rats were ovariectomized. One week later (day 0), they received Silastic capsules containing E2 which produced physiological serum concentrations of E2. Groups of rats were bled sequentially via indwelling right atrial cannulae 1–4 days after capsule implantation (days 1–4). All young rats displayed maximal LH surges by day 2 and exhibited equivalent surges on days 3 and 4. Middle-aged rats required the presence of E2 for at least 3 days before a maximal positive feedback ...

Journal ArticleDOI
TL;DR: It is indicated that prolactin and/or growth hormone are necessary for the development of adjuvant arthritis, whereas adrenocorticotropic hormone has an inhibitory effect.
Abstract: Adjuvant arthritis was induced in female Fisher rats by injecting their right hind paw with 0.1 ml Freund's complete adjuvant. The development of adjuvant arthritis was inhibited by hypophysectomy and by daily treatment of intact animals with the dopaminergic agent bromocriptine. Adjuvant arthritis developed normally if hypophysectomized or bromocriptine-suppressed animals were treated with either prolactin or growth hormone. Additional treatment with adrenocorticotropic hormone inhibited this restoration. Treatment of hypophysectomized rats with follicle-stimulating hormone, luteinizing hormone, and thyroid-stimulating hormone had no effect. These results indicate that prolactin and/or growth hormone are necessary for the development of adjuvant arthritis, whereas adrenocorticotropic hormone has an inhibitory effect.

Journal ArticleDOI
TL;DR: The results show that insulin exerts a direct, specific inhibitory effect on basal and hydrocortisone-induced GH secretion by GH3 cells unrelated to glucose utilization by the cells.
Abstract: The effects of insulin on basal and hydrocortisone-induced growth hormone (GH) secretion were studied in rat pituitary tumor cells (GH3). Cells were grown in monolayer culture and exposed to exogenously added insulin for up to 8 d. Basal GH secretion was inhibited by insulin (0.7 nM) after a 48-h lag period by approximately 50% (P less than 0.01, vs. untreated control cells). The suppression of GH secretion was reversible, as removal of added insulin resulted in return of GH secretion to normal levels after 24 h. Maximal suppression of basal GH secretion was achieved by 0.7 nM insulin, and these effects were prevented by simultaneous exposure of the cells to guinea pig anti-insulin serum (1:2,000). No effects of insulin on cell replication were evident, and glucose concentration in the medium did not differ in control or insulin-treated wells. Insulin (7 nM) significantly suppressed the fivefold hydrocortisone-induced GH stimulation during 5 d of incubation with up to 1,000 nM of the steroid (P less than 0.001). These inhibitory effects were similarly observed in glucose- and pyruvate-free medium, and in the presence of 2-deoxyglucose. Insulin also reversed the suppression of prolactin (PRL) secretion induced by hydrocortisone (1 uM), and actually stimulated basal PRL secretion by over 50%. Insulin did not alter the inhibitory effect of hydrocortisone on GH3 cell proliferation. Although higher doses (13 nM) of insulin-like growth factor (IGF-I) also suppressed basal GH secretion, IGF-I did not alter the GH and PRL secretory changes induced by hydrocortisone. The results show that insulin exerts a direct, specific inhibitory effect on basal and hydrocortisone-induced GH secretion by GH3 cells unrelated to glucose utilization by the cells.

Journal Article
TL;DR: The data suggest that anovulatory cycles are correlated with the amount of exercise and increased levels of catechol estrogens, which may interact to suppress luteinizing hormone release at the hypothalamic pituitary axis.

Journal ArticleDOI
TL;DR: There is insufficient evidence to recommend this drug as primary therapy for either prolactin-secreting or nonfunctional macroadenomas, but the drug may have potential as a preoperative adjunct to effect shrinkage of prolACTinomas and theoretically, at least, make excision easier and possibly more complete.
Abstract: ✓ Bromocriptine inhibits prolactin secretion and causes size reduction of prolactin-secreting adenomas. The effect of the drug upon pituitary tumors other than prolactinomas is uncertain. The authors report a prospective series of 12 patients with pituitary macroadenomas in whom bromocriptine was administered for 6 weeks prior to transsphenoidal surgery. Five of the patients had computerized tomographic documentation of significant reductions in tumor size (Group A) and six had no change (Group B) during 3 and 6 weeks of bromocriptine administration. One patient who demonstrated size reduction in his tumor was not assigned to either group as he was treated with high-dose dexamethasone concurrently with the bromocriptine. Pathological examination (light and electron microscopy and immunocytochemistry) indicated that all Group A patients harbored tumors with prolactin granules whereas all Group B tumors lacked such granules. Adenoma cells in the responsive tumors were involuted with reduced cytoplasmic, nuc...

Journal ArticleDOI
TL;DR: Dietary improvement during lactation alone resulted in these critical prolactin concentrations being reached 21 wk earlier than in nonsupplemented counterparts, while those receiving the extra food in both pregnancy and lactation showed a 35-wk shortening of postpartum amenorrhea and infertility.

Journal ArticleDOI
01 Jun 1984-Brain
TL;DR: The hormonal responses to a generalized tonic-clonic convulsion in 20 patients with idiopathic or posttraumatic epilepsy or alcohol-withdrawal seizures found an increase shortly after the seizure in plasma levels of ACTH, beta endorphin, beta lipotropin, prolactin, and vasopressin and a later increase in plasma cortisol.
Abstract: We studied the hormonal responses to a generalized tonic-clonic convulsion in 20 patients with idiopathic or posttraumatic epilepsy (6 patients) or alcohol-withdrawal seizures (14 patients). We found an increase shortly after the seizure in plasma levels of ACTH, beta endorphin, beta lipotropin, prolactin, and vasopressin, and a later increase in plasma cortisol. There was no significant change in levels of growth hormone, luteinizing hormone, follicular stimulating hormone, or plasma renin activity. An increase in plasma ACTH level was accompanied by a rise in beta lipotropin and beta endorphin, and followed by a rise in plasma cortisol. In 2 patients there was no postictal increase in plasma prolactin, despite changes in other hormones. There was no difference in the nature or time course of the hormonal changes in patients with alcohol-withdrawal seizures and those with seizures from other causes. The mechanisms subserving these changes are unknown. Nonspecific stress influences the release of certain hormones, but the absence of a significant growth hormone response suggests that this was probably not responsible for our findings. It is possible that the generalized neuronal discharge of a seizure stimulates the hypothalamus either directly, through specific neurotransmitter changes, or through the release of other substances. One possibility that we are investigating in experimental animals is that endogenous opioids are involved, especially in the release of prolactin.

Journal ArticleDOI
TL;DR: It is confirmed that the presence of an intact thyroid gland is essential for the development of photorefractoriness and for the release of prolactin which normally follows photostimulation.

Journal ArticleDOI
TL;DR: The responses of serum prolactin (PRL) and growth hormone (GH) to the dopamine agonist apomorphine hydrochloride (0.75 mg subcutaneously) were studied in a large group of unmedicated hospitalized patients with functional psychoses.
Abstract: • The responses of serum prolactin (PRL) and growth hormone (GH) to the dopamine agonist apomorphine hydrochloride (0.75 mg subcutaneously) were studied in a large group of unmedicated hospitalized patients with functional psychoses. There were no differences in the GH response in various diagnostic groups. The PRL response was greater in patients with affective disorders. The GH response was inversely related to total duration of illness in the entire sample of patients, but this correlation was independent of age effect only in the group of patients with major depression. In schizophrenics, the effect of the two factors, age and duration of the illness, could not be separated. The apomorphine-induced GH response was significantly correlated with psychosis ratings and negative symptom scale scores. The apomorphine-induced PRL suppression correlated significantly with various measures of depression across diagnostic groups.

Journal ArticleDOI
TL;DR: It is concluded that GRF is a potent and specific GH secretagogue that also affects specifically GH mRNA levels in normal pituitary cells.
Abstract: A peptide with high intrinsic activity for specifically stimulating the secretion of immunoreactive growth hormone (GH; somatotropin) has been characterized and reproduced by total synthesis. This peptide, human pancreatic growth hormone-releasing factor, 44-amino-acid form (hpGRF1-44-NH2), was isolated from a tumor localized in the pancreas of a patient with acromegaly. We report here the effect of this growth hormone-releasing factor (GRF) on GH release and the GH mRNA levels in monolayer cultures of rat pituitary. The cytoplasmic dot hybridization technique was used to examine the effect of GRF on GH mRNA levels. Incubation of rat pituitary cultures with GRF for 72 hr resulted in a 2- to 2.5-fold increase in GH mRNA levels, and the maximal levels of stimulation were achieved at GRF concentrations as low as 1 fM. GRF did not stimulate prolactin release, nor did it affect specific prolactin mRNA levels in the pituitary cultures. We conclude that GRF is a potent and specific GH secretagogue that also affects specifically GH mRNA levels in normal pituitary cells.

Journal ArticleDOI
TL;DR: The studies showed that there was an acute reduction in the inhibitory effects of endogenous opiates on LH and FSH release following gonadectomy in the rat, and the opiatergic component in the control of gonadotrophin secretion could be reinstated in long-term gonadectomized rats by treatment with oestradiol benzoate or testosterone propionate.
Abstract: We have attempted to clarify the physiological involvement of endogenous opiates in the steroid-mediated control of gonadotrophin release. Our studies showed that there was an acute reduction in the inhibitory effects of endogenous opiates on LH and FSH release following gonadectomy in the rat. This was indicated by a significant reduction in the ability of naloxone to stimulate serum LH/FSH levels (sampled at 15 min) in 26-day-old female rats 48 h after ovariectomy. Luteinizing hormone was highly sensitive to the inhibitory effects of the synthetic met-enkephalin analogue, FK 33-824, at this time (sampled at 90 min). An unexpected observation was that long-term absence of gonadal steroids also disrupted the ability of exogenous opiates, FK 33-824 and morphine, to influence LH release. This was seen as an inability of FK 33-824 (1.0 or 3.0 mg/kg) to inhibit LH secretion. The effects of gonadectomy on opiate control of LH occurred at all developmental stages and were not due to a disruption of sexual maturation. Opiate involvement in prolactin secretion did not appear to be adversely affected by an absence of gonadal steroids. Another novel aspect of this work was that the opiatergic component in the control of gonadotrophin secretion could be reinstated in long-term gonadectomized rats by treatment with oestradiol benzoate or testosterone propionate. Similarly, priming with increasing dosages of oestradiol benzoate which resulted in progressively lower LH levels gave larger naloxone in progressively lower LH levels gave larger naloxone responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Journal ArticleDOI
TL;DR: Although cessation of long-term dopamine agonist therapy leads to recurrence of symptoms and hyperprolactinaemia, rapid tumour regrowth is uncommon and of small extent, and other pituitary function is not altered in the short term.

Journal ArticleDOI
TL;DR: The results of this suggest the occurrence of positive endocrine selection mechanisms operating in vivo on human mammary tumor cell populations, and suggest that concentrations of testosterone or hydrocortisone normally present in body fluids may facilitate the in vivo growth of breast cancer.
Abstract: Individually different growth responses of 10 cell lines newly derived from metastasizing mammary carcinomas were determined by cell counts in experimental incubations with the steroid hormones 17 beta-estradiol, progesterone, testosterone, hydrocortisone (cortisol), the antiestrogenic compound tamoxifen, or prolactin. Of 7 cell lines derived from ductal carcinomas, 5 were stimulated by prolactin. The growth of 4 of 7 cell lines established from the tumors of postmenopausal or ovariectomized patients was enhanced by doses of testosterone, which are in the range of the physiologic serum level. The proliferation of 5 cell lines was promoted by hydrocortisone in the physiologic concentration of 100 nM, supporting the notion that concentrations of testosterone or hydrocortisone normally present in body fluids may facilitate the in vivo growth of breast cancer. The in vitro growth of cells derived from tumors after relapse under treatment with medroxyprogesterone acetate or tamoxifen was markedly enhanced by progesterone or tamoxifen (CAS: 10540-29-1) in concentrations corresponding to therapeutical serum levels and in accordance with in vivo resistance to the endocrine therapy applied before cell sampling. The results of this suggest the occurrence of positive endocrine selection mechanisms operating in vivo on human mammary tumor cell populations.

Journal ArticleDOI
TL;DR: A modification of prolactin, in which the asparagine at position 31 carries a carbohydrate unit, was isolated from ovine pituitary glands and sequence and amino acid analyses identified the point of linkage of the carbohydrate.
Abstract: A modification of prolactin, in which the asparagine at position 31 carries a carbohydrate unit, was isolated from ovine pituitary glands. Sequence and amino acid analyses identified the point of linkage of the carbohydrate. Glucosamine was found in acid hydrolysates, an indication that the carbohydrate is attached through N-acetylglucosamine. The glycosylated prolactin binds to concanavalin A and lentil lectin and is eluted with methyl alpha-D-mannopyranoside. During gel electrophoresis in sodium dodecyl sulfate, the glycosylated hormone migrates as a Mr 25,000 protein; prolactin has a Mr of 23,000. The modified prolactin had a potency of 20 international units/mg, approximately equal to 60% the potency of a reference prolactin preparation when measured by the pigeon crop sac assay. In a radioimmunoassay, the glycosylated form had only 34% the immunoreactivity of ovine prolactin.

Journal ArticleDOI
TL;DR: It might be concluded that adaptation to a repeated stress stimulus is not confined to the pituitary-adrenal axis, however, the degree of adaptation could vary between different hormones.

Journal ArticleDOI
TL;DR: Turnover rates of NE and DA turnover in the medial preoptic/anterior hypothalamic area may be causally related to reduced serum LH levels whereas the reduced hypothalamic DA turnover may explain increased blood prolactin levels.
Abstract: There is some evidence that a population of estrogen-receptive neurons exists in the preoptic/anterior hypothalamic area which uses gamma-aminobutyric acid (GABA) as neurotransmitter and which is involved in mediating the negative feedback of estrogens on pituitary luteinizing hormone (LH) secretion. These neurons are proposed to be presynaptic inhibitors to norepinephrine (NE) release thereby inhibiting the stimulatory effect of NE on LHRH neurons. Muscimol, a potent GABA agonist, inhibits pituitary LH release in ovariectomized rats after intraventricular injection of 5 nmol. This treatment significantly increased prolactin levels. Catecholamine turnover rates in micropunches of various hypothalamic and mesolimbic structures following intraventricular treatment with muscimol were determined using the method of blocking the activity of tyrosine hydroxylase by alpha-methyl-p-tyrosine. Muscimol did not affect catecholamine, GABA and glutamate concentrations. Turnover rates of NE were significantly reduced in the medial preoptic/anterior hypothalamic area. In this structure as well as in the nucleus accumbens and in the anterior mediobasal hypothalamus turnover rates of dopamine (DA) were also reduced whereas DA turnover in mediocortical amygdalae was increased by muscimol. The selective reduction of NE turnover following muscimol may be explained by a direct or indirect action of the GABA-eric drug on NE axon terminals. The reduced NE and DA turnover in the medial preoptic area may be causally related to reduced serum LH levels whereas the reduced hypothalamic DA turnover may explain increased blood prolactin levels.

Journal ArticleDOI
TL;DR: The results indicate that the induction of GH and PRL receptors by rGH occurs independently of SM-C generation, but suggest that newly induced GH receptors in GH-treated hypophysectomized rats may be involved in SM- C generation.
Abstract: To determine whether induction of rat liver GH and PRL receptors by GH infusion is dependent upon the sex of the animal or whether or not the pituitary is intact, rat GH (rGH) or rat PRL (rPRL) was infused at approximately 200 μg/day for 7 days into male and female, intact and hypophysectomized rats, and the binding of radioiodinated bovine GH (bGH) and ovine PRL (oPRL) to liver microsomal membranes was measured. In females, bGH binding was reduced by hypophysectomy whether or not membranes were MgCl2 treated to remove endogenous ligand. However, in males, hypophysectomy caused an apparent 3-fold induction of bGH binding sites, which was absent in MgCl2-treated membranes, suggesting that the effect was due to receptor occupancy by endogenous rGH in the intact males. Hypophysectomy also lowered oPRL binding in females but had no effect in males. Infusion of rGH significantly induced binding sites for bGH and oPRL in all treatment groups, independently of sex or the presence of the pituitary, whereas rPRL i...