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Biomedical subjects

G Fink

Publications and source records attributed to G Fink.

At least 181 records · Page 10Linked to original sources
PubMed1986

Prolactin messenger ribonucleic acid levels in the normal and hypogonadal mouse pituitary gland.

The effects of estrogen on the synthesis of pituitary PRL mRNA and PRL and the release of PRL into plasma were investigated in male and female normal and hypogonadal (hpg) mice. Because the hpg mouse is totally deficient in hypothalamic GnRH, it provides an excellent model for investigating the effects of estrogen and GnRH on PRL synthesis and release in the presence of a totally inactive gonadotropin-gonadal system. Estrogen stimulated the synthesis and release of pituitary PRL in both sexes of normal and hpg mice, and this marked increase in PRL synthesis correlated with an equally dramatic increase in pituitary PRL mRNA levels. Administration of GnRH alone produced a slight but significant increase in pituitary PRL content, which is consistent with an action of GnRH on prolactotropes, either directly or by way of a paracrine action involving gonadotropes.

Animals↗
PubMed1986

Postnatal ovarian follicle development in hypogonadal (hpg) and normal mice and associated changes in the hypothalamic-pituitary ovarian axis.

Significant uterine growth occurred in normal and hypogonadal (hpg) mice between Days 7 and 21 but thereafter no further growth was observed in hpg mice. The ovaries of hpg mice were significantly smaller than those of normals at all ages, but there was no significant difference between the number of non-growing follicles in the ovaries of mutants and their normal littermates at any age studied, and normal and hpg mice showed a marked reduction in the number of non-growing follicles during the first month of life. The size and composition of the growing follicle population in hpg mice, however, differed markedly from those in normal animals and by 21 days of age the number of growing follicles in mutants was significantly reduced. There was no significant difference in the number of Type 3b follicles before 60 days of age, but the number of all other follicle types was significantly less in hpg mice at all ages studied. Follicles in which the antrum is fully developed (Type 7 and 8) were never seen in the ovaries of mutants and corpora lutea were never observed. Interstitial tissue development was also very poor in hpg ovaries. The hypothalamic GnRH content in normal mice remained low until Day 20, before rising sharply to adult levels (approximately 800 pg) between Days 20 and 30. The pituitary FSH content increased over the first 10 days of life to reach a peak of about 5000 ng, before declining to the adult value of about 2000 ng by Day 30, whilst the plasma FSH concentration was high in the first 10 days, but fell to adult levels over the next 20 days. Pituitary LH content increased significantly between Days 5 and 10 to reach the adult level of about 600 ng. Hypothalamic GnRH was undetectable at all ages in hypogonadal mice, but the pituitary content of FSH and LH had risen to the attenuated mutant adult value by Day 15, and unlike normals, plasma FSH concentrations were not elevated during the neonatal period. These results suggest that minimal gonadotrophic stimulation of the ovary from birth has no effect on the total number of follicles but reduces the number of growing follicles and prevents follicle growth beyond the early antral stage. Gonadotrophins therefore appear to have a role in the initiation and continuance of follicle growth in the adult mouse.

Animals↗
PubMed1986

Changes in the granule population of gonadotrophs of hypogonadal (hpg) and normal female mice associated with the priming effect of LH-releasing hormone in vitro.

Changes in the size and position of secretory granules in pituitary gonadotrophs have been studied in relationship to LH release and self-priming induced by LH-releasing hormone (LHRH) in pituitary glands from normal and hypogonadal (hpg) female mice. Hemipituitary glands were preincubated and then incubated for either 1 or 2 h in the absence or presence of LHRH (8.5 nmol/l). The glands were either processed for ultrastructural morphometry or homogenized for the determination of pituitary LH content. Morphometry was carried out on gonadotrophs identified by immunocytochemistry for LH beta using the thin/semi-thin section method. Pituitary LH content and the amount of LH released were determined by radioimmunoassay. The amount of LH released in response to the first and second hours of incubation with LHRH were similar in hpg and normal mice with a clear priming effect (three- to fourfold increase in pituitary responsiveness to LHRH) occurring in both strains. Despite a substantially reduced total number of granules (and amount of LH) in unstimulated hpg gonadotrophs, the number of granules in the outer 500 nm marginal zone of the cells was similar to that in normal mice. This could explain the similar amount of LH released from normal and hpg glands by the first LHRH challenge. The initial exposure to LHRH was also associated with a marked translocation of secretory granules from the central to the outer marginal region of cytoplasm subjacent to the gonadotroph plasmalemma, such that in 'primed' glands 60% of granules were found in this marginal zone compared with 40% (hpg) or 33% (normal) in unstimulated glands. The mean diameter of granules in the marginal zone was significantly less than that of granules in the central zone of the gonadotrophs of unstimulated glands from both normal and hpg animals. Exposure to LHRH for 1 h was associated with an increase in the number of small granules in the marginal zone and a significant decrease in the mean diameter of the gonadotroph granule population as a whole. After the primed release of LH, increased proportions of granules were still located in the marginal zone of gonadotrophs, indicating that granule migration continued during the second hour of exposure to LHRH in which primed release occurred. The primed release was associated with a detectable reduction in both the LH and granule content of gonadotrophs in normal, but not hpg glands.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

The short-term effects of testosterone on brain protein synthesis in 4-day-old rats: an electrophoretic study of proteins following intraventricular injection of [35S]methionine.

The short-term effects of administering testosterone propionate (TP) to 4-day female rats (androgenized females) on the synthesis of specific brain proteins were investigated. At various times after the intraperitoneal injection of TP or arachis oil, [35S]methionine was injected into the third ventricle and 1 h later proteins were extracted from the hypothalamus-preoptic area (H-POA) and analyzed by sodium dodecyl sulphate polyacrylamide gel electrophoresis. Changes in synthesis of two 13,000-14,000 mol. wt. proteins in the 4-day rat brain were detected, and these changes appeared to be specific for the H-POA. In addition, silver staining revealed a 50,000 mol. wt. protein which was present in the male and androgenized female H-POA but not in the oil-treated female H-POA. An incidental, but potentially important finding, was the synthesis of a 77,600 mol. wt. protein in the H-POA of one animal which had several seizures during the experiment. These results show that changes in the synthesis of specific proteins occur in the H-POA of neonatal female rats within 8 h of TP administration and support the hypothesis that hormone-induced changes in brain protein synthesis may be involved in sexual differentiation of the brain.

Animals↗
PubMed1985

LH-RH in the rat and mouse hypothalamus and rat hypophysial portal blood: confirmation of identity by high performance liquid chromatography.

The nature of the immunoreactive (IR) form of luteinizing hormone-releasing hormone (LH-RH) in rat hypophysial portal vessel blood and in extracts of hypothalamus from rats and normal and hypogonadal (hpg) mice was investigated using high performance liquid chromatography and two highly specific anti-LH-RH sera. In rat hypophysial portal blood and in hypothalamic extracts from rats and normal mice a single immunoreactive peak was present which corresponded in retention time to synthetic LH-RH. No LH-RH-IR was detected in hypothalamic extracts from the hpg strain of mouse.

Animals↗
PubMed1985

Effects of water deprivation and deamino [8-D-arginine] vasopressin on [14C]2-deoxyglucose uptake by the hypothalamo-hypophysial system in mice with hereditary nephrogenic diabetes insipidus.

The effects of water deprivation and the injection of deamino [8-D-arginine] vasopressin (dDAVP) on the metabolic activity of the hypothalamo-neurohypophysial neurones of mice with inherited nephrogenic diabetes insipidus (DI +/+ Severe) have been investigated by quantitative autoradiography using the [14C]2-deoxyglucose (2-DG) technique. The relative metabolic activities (rma) of the paraventricular nuclei (PVN) and pars nervosa (PN) in severely diabetic mice were not significantly different from the rma of the PVN and PN in Non-severe or Normal mice, but the rma of the pars distalis (PD) was greater in the Severe mice than in the other two strains. Water deprivation (4-5 h) significantly increased the rma of the PVN and PN in Severe mice compared with those in Non-severe mice that had been similarly deprived of water. The increased rma of the PVN and PN produced by water deprivation in Severe mice was not reduced to normal by injection of dDAVP. The injection of dDAVP alone had no effect on the rma of the PVN or PN, but dDAVP injection alone, water deprivation alone, or both treatments combined decreased the rma of the PD in Severe mice. Neither the supraoptic nuclei (SON) nor any of the other 19 brain areas studied were affected, in terms of rma, by either water deprivation, injection of dDAVP, or both.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Effects of intravenously administered 6-hydroxydopamine on the content of monoamines in the median eminence and neurointermediate lobe of the rat.

The effects of intravenous administration of 6-hydroxydopamine (6-OHDA) on the content of catecholamines in the median eminence and neurointermediate lobe was studied in male rats. The results confirmed previous findings of a depletion of catecholamines in both regions as a result of this lesion, although the magnitude of the effect was less than that revealed by fluorescence histochemistry. Administration of desipramine before 6-OHDA injection produced a more specific lesion, depleting dopamine but leaving noradrenaline unaffected.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

Selective increase in plasma luteinising hormone concentrations in drug free young men with mania.

The hypothalamic-pituitary-gonadal system was investigated in drug free young men with either mania or acute schizophrenia and in age matched controls by measuring, at frequent intervals during a 17 hour "neuroendocrine day," plasma concentrations of luteinising hormone (LH), follicle stimulating hormone, prolactin, testosterone, sex hormone binding globulin (SHBG), and cortisol. Plasma LH in mania was significantly increased compared with the control value at all time periods and increased in the morning and evening samples compared with values in the schizophrenic patients. Plasma prolactin and cortisol concentrations were significantly greater in mania and schizophrenia compared with control values at several times during the day, but there were no significant between group differences in plasma testosterone or SHBG. These results show that in young men with mania there is a major disturbance in the central mechanisms that control the release of LH, the control of prolactin and cortisol secretion is abnormal in mania and acute schizophrenia, and plasma LH concentrations may provide a useful hormonal diagnostic test for mania.

Adolescent↗
PubMed1985

Neurotensin immunoreactivity in post-mortem brain is increased in Down's syndrome but not in Alzheimer-type dementia.

Neurotensin immunoreactivity and choline acetyltransferase (ChAT) activity were measured in post-mortem brain from 10 cases of Down's syndrome (7 aged 53-63 years, one aged 27 years, one aged 16 months and one aged 10 months), 6 cases of Alzheimer-type dementia (ATD) and 19 control subjects (13 aged 40-88 years and 6 aged 9-18 months). Neurotensin concentrations in anterior and basal hypothalamus, amygdala, septal area, caudate nucleus and temporal cortex were unaltered in ATD. The concentrations of neurotensin were significantly increased in the caudate nucleus, temporal cortex and frontal cortex in the cases of Down's syndrome aged 53-63 years with the neuropathological features of ATD, and were also increased in the cerebral cortex of the 27-year-old, which did not have the neuropathological features of ATD, and in two infant Down's cases. ChAT activity was reduced in the ATD and the 53-63-year-old cases of Down's syndrome, but not in the 27-year or 10-month-old Down's cases. The increased neurotensin concentrations appear to be a feature of Down's syndrome not related to the presence of plaques and neurofibrillary tangles or to a deficit in ChAT activity.

Adult↗
PubMed1985

Effects of progesterone on the pituitary responsiveness to, and priming effect of luteinizing hormone releasing hormone in female rats exposed to constant light.

We have investigated the role of progesterone in the mating-induced release of luteinizing hormone (LH) and ovulation in female rats exposed to a 60-day period of constant light (LL). Plasma LH and progesterone concentrations were increased after mating; plasma estradiol concentrations, although not increased after mating, were increased compared with the concentrations in female rats on light-dark (LD) exposure during diestrus, proestrus evening and estrus. Progesterone induced ovulation in about half the number of female rats exposed to long-term LL, and in these animals, there was a significant increase in pituitary responsiveness to luteinizing hormone releasing hormone (LHRH) 5 h after progesterone injection. The magnitude of the priming effect of LHRH was markedly increased 2 h after progesterone treatment. Treatment with sodium pentobarbitone (SP) 15 min before an injection of progesterone, blocked the increase in pituitary responsiveness to LHRH 5 h later, but treatment with SP 4 h before progesterone injection did not block the increase in the magnitude of the priming effect of LHRH. These results suggest that progesterone acts both at the brain and pituitary to facilitate LH release, and that the increase in plasma progesterone produced by mating is at least partly responsible for the LH surge induced by mating in LL rats.

Animals↗
PubMed1985

Choline acetyltransferase activity in the pars distalis, preoptic area and striatum during the rat estrous cycle.

Choline acetyltransferase (CAT) activity of the striatum, preoptic area (POA), and pars distalis (PD) of the anterior pituitary gland was measured on each day of the 4-day estrous cycle of adult Wistar rats. Only in the PD did CAT activity vary significantly during the cycle, with the activity being lower during estrus than at other stages of the cycle. The CAT activity of the PD was extremely low, approximately 500 nmol/h/g protein, and, therefore, the specificity of the CAT activity of the PD was verified in studies on substrate requirement, the effect of a CAT inhibitor, and by paper chromatography of the reaction products. Measurement of CAT activity in saline-perfused glands, in sections of tissue taken from the lateral extremes of the PD and in hypophysial portal blood showed that the CAT activity of the PD was intrinsic, and not due to CAT activity in entrapped blood or adjacent tissues. The precise cellular origins of CAT in PD and the significance of the cyclical variation require further investigation.

Animals↗
PubMed1985

Effects of hyperprolactinaemia and testosterone on the release of LH-releasing hormone and the gonadotrophins in intact and castrated rats.

We have investigated the effect of hyperprolactinaemia on the secretion of LH-releasing hormone (LHRH), LH and FSH in male rats of the PVG strain which were left intact, castrated or castrated and then implanted with either a 10 or 30 mm silicone elastomer capsule containing testosterone (T10 and T30 respectively). Hyperprolactinaemia was produced by pituitary grafts under the kidney capsule. Pituitary stalk blood, for LHRH estimation, and peripheral blood, for LH, FSH and prolactin, were collected under alphaxalone anaesthesia. Pituitary stalk blood was collected during three consecutive periods of 30 min each before, during and after the application of an electrical stimulus to the median eminence (ME). Hyperprolactinaemia significantly reduced the plasma concentrations of FSH in intact rats and the post-castration increase in the plasma concentrations of both LH and FSH. Neither hyperprolactinaemia nor castration had any significant effect on the spontaneous output of LHRH, but castration alone or castration plus implantation of a T30 capsule did significantly reduce the increment in LHRH output produced by ME stimulation, an effect not seen in rats bearing pituitary grafts. The T30, but not the T10 capsules suppressed the post-castration increase in the gonadotrophins, and the inhibitory effect of testosterone was not significantly affected by hyperprolactinaemia. An incidental but important finding was that the presence of pituitary grafts under the kidney capsule reduced the anaesthetic dose of alphaxalone by 63%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Effects of antiserum to thyrotrophin-releasing hormone on the concentrations of plasma prolactin, thyrotrophin and LH in the pro-oestrous rat.

The possible role of thyrotrophin-releasing hormone (TRH) in causing the pro-oestrous surge of prolactin was investigated in conscious female rats by passive immunization with a specific anti-TRH serum raised in sheep. Blood samples were withdrawn through a previously implanted intra-atrial cannula. The i.p. injection of 1 ml anti-TRH serum, but not non-immune sheep serum, at 13.00 h of pro-oestrus delayed by about 1 h the onset of the prolactin surge, but the peak of the surge was similar to that in animals injected with the non-immune serum. The plasma concentrations of TSH were significantly reduced by the anti-TRH serum, but plasma concentrations of LH were not significantly affected. These results show that TRH may play an important role in the timing and initiation, but not the maintenance of the prolactin surge in the pro-oestrous rat.

Animals↗
PubMed1985

Oxytocin and vasopressin in rat hypophysial portal blood: experimental studies in normal and Brattleboro rats.

Oxytocin (OT) and vasopressin (VP) were measured by radioimmunoassay in hypophysial portal and peripheral blood from male Wistar rats and heterozygous and homozygous Brattleboro rats anaesthetized with urethane. In Wistar rats the concentrations of OT and VP were about 50 times greater than the concentrations in peripheral blood, whether or not the pituitary gland was left in situ during collection, and also considerably greater than the reported concentrations of the peptides in the cerebrospinal fluid. The release of both peptides was increased significantly by a lesion of the supraoptico-hypophysial tract that led to diabetes insipidus, but which left intact the external layer of the median eminence (ME). Concentrations of VP were undetectable in plasma from homozygous Brattleboro rats, but the portal plasma concentrations of VP in heterozygous Brattleboro rats were not significantly lower than in Wistar rats. The concentrations of OT in portal plasma from both types of Brattleboro rat were significantly higher than in Wistar rats. The output of VP and OT into hypophysial portal blood of Wistar rats was not significantly affected by electrical stimulation of the suprachiasmatic, supraoptic or paraventricular nuclei or the ME using two types of stimuli, one of which produced an increase in peripheral plasma concentrations of VP and OT in intact rats and a significant increase in the release of LH-releasing hormone into hypophysial portal blood. The output of VP and OT into portal blood was also not significantly affected by either adrenalectomy with or without injection of dexamethasone or the injection of either the 5-hydroxytryptamine (5-HT) synthesis blocker, parachlorophenylalanine, or the 5-HT uptake blockers, alaproclate or zimelidine. These results show that large amounts of OT as well as VP are released into hypophysial portal blood from fibres of the hypothalamo-neurohypophysial system that terminate in the external layer of the ME. Although distinct from the fibres that terminate in the pars nervosa (PN), the findings in Brattleboro rats show that the VP fibres of the ME system originate in neurones with a genomic mechanism for VP synthesis similar to that of the VP neurones that project to the PN. The lack of effect of adrenalectomy and the administration of 5-HT synthesis and uptake blockers must be interpreted with caution since the results obtained with electrical stimulation suggest that when the pituitary stalk is cut the release of OT and VP into portal blood approaches a maximum and may therefore be difficult to alter by experimental manipulation.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenalectomy↗
PubMed1985

Effects of 5-hydroxytryptamine uptake blockers on the release of LH and prolactin in several different experimental steroid models in the rat.

The effect of the 5-hydroxytryptamine (5-HT) uptake blockers on the surges of LH and prolactin has been investigated in pro-oestrous rats and various experimental models used frequently to study the effects of steroids on LH and prolactin secretion in female rats. The steroid models were: rats ovariectomized on dioestrus, injected immediately with oestradiol benzoate (OB) and at 12.00 h on the next day (presumptive pro-oestrus) with progesterone (model 1); long-term ovariectomized rats injected with a single injection of OB and 72 h later with either progesterone (model 2) or OB (model 3); long-term ovariectomized rats injected daily with OB (model 4). The uptake blockers alaproclate (3-30 mg/kg) and zimelidine (20 mg/kg) were injected and blood samples withdrawn from previously implanted intra-atrial cannulae. Plasma LH and prolactin concentrations were determined by radioimmunoassay. The present study confirmed that a surge of LH occurs at about 17.00-18.00 h of the presumptive day of pro-oestrus in model 1, at about 5 h after (approximately 17.00 h) the injection of either progesterone or the second injection of OB in models 2 and 3, and diurnally in model 4, and the simultaneous occurrence of a prolactin surge in models 2 and 4. A surge of prolactin at the same time as the LH surge was shown to occur also in models 1 and 3. Alaproclate (30 mg/kg) administered at 15.00 h delayed significantly the peak of the prolactin surge in the pro-oestrous rat and models 1, 3 and 4, and in the latter the magnitude of the prolactin surge was also significantly reduced. By contrast, the peak of the prolactin surge in model 2 was significantly prolonged by alaproclate. Alaproclate had no significant effect on either the timing or the magnitude of the LH surge in the pro-oestrous rat, and models 3 and 4. The peak of the LH surge was delayed by alaproclate in model 1 and abolished in model 2, providing further evidence for the possible importance of interactions between 5-HT and progesterone in neuroendocrine control. Zimelidine had no significant effect on either the LH or prolactin surge in the pro-oestrous rat and in models 1 and 2. These results show that normal 5-HT uptake is necessary for the normal timing and/or magnitude of the spontaneous and steroid-induced prolactin surge but is not essential for the normal timing and magnitude of the spontaneous surge of LH and the LH surge in some but not all steroid models.(ABSTRACT TRUNCATED AT 400 WORDS)

Alanine↗
PubMed1985

Parachlorophenylalanine blocks the spontaneous pro-oestrous surge of prolactin as well as LH and affects the secretion of oestradiol-17 beta.

The effect of the 5-hydroxytryptamine synthesis inhibitor, parachlorophenylalanine (PCPA), on the spontaneous, pro-oestrous surges of prolactin and LH was investigated in conscious female rats implanted with an intra-atrial cannula. The LH surge was blocked in all animals treated with PCPA, but the prolactin surge was blocked in six out of ten animals and unaffected in four out of ten animals. There was a significant correlation between the plasma concentrations of prolactin and oestradiol-17 beta, surges of prolactin occurred in animals with plasma oestradiol-17 beta concentrations of 120 pmol/l and above, and the LH surge was blocked in animals in which the oestradiol-17 beta concentration was less than 188 pmol/l plasma. These results show that (i) PCPA can block the pro-oestrous prolactin as well as the LH surge, (ii) in addition to a central action PCPA may depend also on its peripheral effect on the secretion of oestradiol-17 beta and (iii) on average, lower plasma concentrations of oestradiol-17 beta are required for triggering the prolactin compared with the LH surge.

Animals↗