Search Results
Search for other papers by KANJI SEIKI in
Google Scholar
PubMed
Search for other papers by MASAKAZU HATTORI in
Google Scholar
PubMed
Short-term experiments (Seiki, Higashida, Imanishi, Miyamoto, Kitagawa & Kotani, 1968; Seiki, Miyamoto, Yamashita & Kotani, 1969) have failed to show any specific progesterone-binding receptors in the hypothalamus and pituitary gland. These sites do not show selective uptake of progesterone compared with other parts of the brain after i.v. administration of [3H]progesterone to rats in various experimental conditions. To investigate more extensively the existence of specific receptor sites in the hypothalamus and pituitary gland, a long-term experiment was carried out.
Female Wistar rats, weighing about 230 g, were used. Ovariectomy was carried out only on animals in dioestrus, as determined by vaginal smears. Two to three weeks after the operation, the animals were given an i.v. injection of 50 μCi [7α-3H]progesterone/100 g body weight (sp. act. 18·1 Ci/μmol) in 0·2 ml 0·9% NaCl solution containing 5% (v/v) ethanol. The animals were killed by decapitation at varying intervals of
Search for other papers by D Olchovsky in
Google Scholar
PubMed
Search for other papers by J F Bruno in
Google Scholar
PubMed
Search for other papers by M Berelowitz in
Google Scholar
PubMed
Abstract
Growth hormone-releasing factor (GRF) mRNA expression in male rats occurs predominantly in the hypothalamus (mainly in the arcuate nucleus), and among extraneural sites primarily in the testis. Hypothalamic GRF is the physiological tropic stimulus to growth hormone secretion. However, the role of GRF in the testis is unknown. We have shown previously that hypothalamic GRF mRNA expression is significantly reduced in streptozotocin (STZ)-diabetic rats. This reduction is confined to the arcuate nucleus and probably accounts for the suppression of growth hormone pulsatility.
The present studies were performed to evaluate GRF expression in the testis of streptozotocin (STZ)-diabetic rats. Diabetes was induced by injection of STZ (100 mg/kg i.p.). Seventeen to twenty days later diabetic rats were hyperglycemic compared with vehicle-injected controls and demonstrated growth failure. Insulin treatment reduced the glycemia and increased body weight towards normal. Total RNA was extracted from the hypothalamus and testis, and GRF mRNA levels estimated by solution hybridization/nuclease protection assay. Levels of hypothalamic somatostatin mRNA were measured to serve as control values. GRF mRNA was significantly (P<0·001) decreased in the hypothalamus of STZ-diabetic rats (0·2 ± 0·07 mean relative densitometric units, n=8) compared with controls (1·0 ± 0·19, n=8) with no change in somatostatin mRNA expression. In contrast, testicular GRF mRNA was increased 70% (P<0·05) in STZ-diabetic rats. Insulin treatment resulted in normalization of hypothalamic GRF mRNA levels (1·1 ± 0·17, n=5) with no effect on testicular GRF mRNA expression.
In conclusion GRF gene expression is discordantly regulated in tissues of male STZ-diabetic rats. While reduced GRF expression may account for the low growth hormone state in this model, increased testicular GRF mRNA (with the previously reported reduction of insulin-like growth factor-I mRNA) resembles the response seen in growth hormone-sensitive tissue (especially the hypothalamus) to this growth hormone-deficient state.
Journal of Endocrinology (1996) 148, 189–192
Search for other papers by AI Turner in
Google Scholar
PubMed
Search for other papers by AJ Tilbrook in
Google Scholar
PubMed
Search for other papers by IJ Clarke in
Google Scholar
PubMed
Search for other papers by CJ Scott in
Google Scholar
PubMed
We tested the hypotheses that progesterone enhances the negative feedback actions of testosterone in rams and that this occurs through actions at the hypothalamus. In the first part of this study, blood samples were collected every 10 min for 12 h before and after 7 days of treatment (i.m.) of castrated Romney Marsh rams (n=5 per group) with vehicle, progesterone (4 mg/12 h), testosterone (4 mg/12 h) or a combination of progesterone (4 mg/12 h) and testosterone (4 mg/12 h). In the second part of this study the brains of four gonad-intact Romney Marsh rams were collected, the hypothalamus was sectioned and in situ hybridisation of mRNA for progesterone receptors conducted. After 7 days of treatment with vehicle or progesterone or testosterone alone, there were no changes in the secretion of LH. In contrast, treatment with a combination of progesterone and testosterone resulted in a significant (P<0.01, repeated measures ANOVA) decrease in mean plasma concentrations of LH, the number of LH pulses per hour and the pre-LH pulse nadir and a significant (P<0.01) increase in the inter-LH pulse interval. We found cells containing mRNA for progesterone receptors throughout the hypothalamus, including the preoptic area (where most GnRH neurons are located in sheep), the periventricular, ventromedial and arcuate nuclei and the bed nucleus of the stria terminalis. This study shows that progesterone is capable of acting centrally with testosterone to suppress the secretion of LH in castrated rams and that cells containing mRNA for progesterone receptors are located in the hypothalamus of rams in the vicinity of GnRH neurons.
Search for other papers by M. GINSBURG in
Google Scholar
PubMed
Search for other papers by N. J. MACLUSKY in
Google Scholar
PubMed
Search for other papers by I. D. MORRIS in
Google Scholar
PubMed
Search for other papers by P. J. THOMAS in
Google Scholar
PubMed
SUMMARY
High-affinity binding of [2,4,6,7-3H]oestradiol-17β has been studied in cytosols prepared from hypothalami, pituitaries and uteri of female rats killed at different stages of the oestrous cycle, and in cytosols prepared from the hypothalami and pituitaries of male rats. In all cases the equilibrium dissociation constant of reaction was of the order of 10−10 mol/l. The number of available high affinity sites per tissue (n) varied with physiological state. In females, n fluctuated with the oestrous cycle. In hypothalamus and pituitary, n fell by about 60 and 40% respectively in pro-oestrus, replenishment occurred during oestrus but could be delayed by phenobarbitone administration during the afternoon of pro-oestrus. In the uterus, n varied biphasically, there being peaks during dioestrus and oestrus, and troughs at pro-oestrus and metoestrus. The numbers of available sites at metoestrus were 12·5 × 109, 10·6 × 1010 and 24·4 × 1010 for hypothalamus, pituitary and uterus respectively. In male rats, values for n were similar to those obtained for females at pro-oestrus (n/hypothalamus = 6·8 × 109, n/pituitary = 4·2 × 1010). Binding was oestrogen specific in all the tissues studied.
Search for other papers by S. M. Cockle in
Google Scholar
PubMed
Search for other papers by J. M. Morrell in
Google Scholar
PubMed
Search for other papers by D. G. Smyth in
Google Scholar
PubMed
ABSTRACT
TRH-related peptides were extracted from the hypothalamus and prostate gland of the rabbit. The peptides were fractionated by gel exclusion chromatography and located by trypsin digestion and radioimmunoassay with antibodies to TRH amide and TRH–Gly Lys. In the hypothalamus TRH-related peptides containing approximately 16 and 30 residues were observed: in these peptides the extensions to the TRH sequence were exclusively in the C-terminal direction. In addition, the three-residue form of TRH was also present. In the prostate complex, the predominant TRH-related peptide contained approximately 50 residues and the extension to the TRH tripeptide was on the N-terminal side; a three-residue form of immunoreactive TRH was also demonstrated. The same pattern of TRH-related peptides was shown to be present in rabbit semen. The results reveal the existence of a novel TRH-related polypeptide in the prostate and semen which does not occur in the hypothalamus. This peptide appears to undergo secretion.
Journal of Endocrinology (1989) 120, 31–36
Search for other papers by A Boelen in
Google Scholar
PubMed
Search for other papers by J Kwakkel in
Google Scholar
PubMed
Search for other papers by DC Thijssen-Timmer in
Google Scholar
PubMed
Search for other papers by A Alkemade in
Google Scholar
PubMed
Search for other papers by E Fliers in
Google Scholar
PubMed
Search for other papers by WM Wiersinga in
Google Scholar
PubMed
During illness, major changes in thyroid hormone metabolism and regulation occur; these are collectively known as non-thyroidal illness and are characterized by decreased serum triiodothyronine (T(3)) and thyroxine (T(4)) without an increase in serum TSH. Whether alterations in the central part of the hypothalamus-pituitary-thyroid (HPT) axis precede changes in peripheral thyroid hormone metabolism instead of vice versa, or occur simultaneously, is presently unknown. We therefore studied the time-course of changes in thyroid hormone metabolism in the HPT axis of mice during acute illness induced by bacterial endotoxin (lipopolysaccharide; LPS).LPS rapidly induced interleukin-1beta mRNA expression in the hypothalamus, pituitary, thyroid and liver. This was followed by almost simultaneous changes in the pituitary (decreased expression of thyroid receptor (TR)-beta2, TSHbeta and 5'-deiodinase (D1) mRNAs), the thyroid (decreased TSH receptor mRNA) and the liver (decreased TRbeta1 and D1 mRNA). In the hypothalamus, type 2 deiodinase mRNA expression was strongly increased whereas preproTRH mRNA expression did not change after LPS. Serum T(3) and T(4) fell only after 24 h.Our results suggested almost simultaneous involvement of the whole HPT axis in the downregulation of thyroid hormone metabolism during acute illness.
Search for other papers by Sonia Aratan-Spire in
Google Scholar
PubMed
Search for other papers by Kari Moilanen in
Google Scholar
PubMed
Search for other papers by Paul Czernichow in
Google Scholar
PubMed
Thyrotrophin releasing hormone-degrading activity (TRH-DA) is present in plasma, hypothalamus, pituitary gland, liver and kidney of adults of several species. Each of these tissues contains more than one TRH-degrading enzyme but only one, pyroglutamate aminopeptidase, isolated from the blood, is a TRH-specific enzyme.
The aim of this study was to describe the developmental pattern of TRH-DA in the plasma, hypothalamus and liver and the role of tri-iodothyronine (T3) in the development of TRH-DA in the rat. Based on the hypothesis that thyroid hormones stimulate plasma TRH-DA in adult rats, degradation of TRH was studied in hypo- or hyperthyroid rats induced by 6-n-propyl-2-thiouracil or T3 respectively.
Tritiated TRH was incubated with plasma and homogenates of hypothalamus or liver. After separation of degradation products by thin-layer chromatography, the amount of degraded [3H]TRH (pmol/50 μl plasma or homogenate) was taken as a comparative index of TRH-DA.
Plasma TRH-DA was not detectable before day 9 while hypothalamic and hepatic TRH-DA was already active at birth. Furthermore, the maturation pattern of total TRH-DA was different in plasma compared with other tissues and T3 appeared to play a significant role in its development.
The absence of plasma TRH-DA in the neonatal period, its special thyroid-dependent developmental pattern and the presence of a specific TRH-degrading enzyme in adult blood suggest a physiological regulatory role for this activity.
Search for other papers by F. J. C. M. Van Eerdenburg in
Google Scholar
PubMed
Search for other papers by C. M. J. E. Lugard-Kok in
Google Scholar
PubMed
Search for other papers by D. F. Swaab in
Google Scholar
PubMed
ABSTRACT
Postnatal development of the supraoptic nucleus (SON) in the pig hypothalamus was studied morphometrically. The volume of the SON increased from 6·2±0·45 (s.e.m.) mm3 at 7 weeks postnatally to 18·5 ± 1·35 mm3 at 2·5 years of age. A sex difference was found at the development point when the SON volume increased, with earlier SON enlargement in males. This sex difference was 30% at 30 weeks and 50% at 1 year of age. At 2·5 years of age no difference in volume was apparent between the sexes. The number of SON neurones was similar for all age groups concerned (43 500 ± 1475), except for the 2·5year-old females where 40% more were found (55 500 ± 3285). No significant difference was found in neurone number between gonadectomized and sham-operated animals, but the operation caused a 30% reduction in the number of neurones and SON volume. Testosterone supplementation following gonadectomy, during the first 4 weeks postnatally, resulted in sexual dimorphism, the males having more SON neurones than the females. The volume showed only a trend in the same direction. Testosterone supplementation at other ages did not result in any difference when compared with controls.
The results of this study show that the postnatal development of the SON of the pig is sexually dimorphic, and that it continues after puberty in females. In contrast to the vasopressin- and oxytocincontaining nucleus, the development of the SON was not influenced by gonadectomy and only slightly by gonadal steroids.
Journal of Endocrinology (1992) 134, 19–25
Search for other papers by T. Watabe in
Google Scholar
PubMed
Search for other papers by M. L. Levidiotis in
Google Scholar
PubMed
Search for other papers by B. Oldfield in
Google Scholar
PubMed
Search for other papers by E. M. Wintour in
Google Scholar
PubMed
ABSTRACT
In previous studies, using one particular antibody, immunohistochemical localization of corticotrophin-releasing factor (CRF) in ovine fetal brain was not possible before 90 days of gestation (term is approximately 150 days), although radioimmunoassay of hypothalamic extracts, using a different antibody, had shown CRF to be present from 63 days. The purpose of this study was to use a variety of CRF antibodies in both immunohistochemistry and radioimmunoassay to determine the presence and concentration of the CRF peptide as early in gestation as possible, and to determine whether more than one molecular size of CRF is detectable at any time in gestation. Seven different antibodies were used on hypothalamic tissue or extracts from seven adult sheep and 37 fetuses from 48 to 140 days of gestation. With one ovine CRF antibody (provided by Dr W. Vale, Salk Institute) immunohistochemical detection of CRF-labelled neurones and nerve fibres of the paraventricular nucleus and median eminence was possible from 49 days. The antibody with the greatest sensitivity in radioimmunoassay was one raised against human CRF, Ab-code R1 (provided by Dr E. Hillhouse, University of Newcastle upon Tyne). The hypothalamic contents of CRF (ng/whole hypothalamus) were 0·28±0·06 (mean ± s.e.m.) (n = 4), 9·0±0·6 (n = 5), 14·3±0·6 (n = 5), 30·0±3·4 (n = 4) in fetuses at 48–50, 100–109 and 139–140 days of gestation and in adult sheep respectively. At all ages only one peak of CRF-like activity, which co-eluted with synthetic ovine CRF, was observed after chromatography of hypothalamic extracts, and assays performed with three different antibodies. Thus there are small amounts of CRF in the ovine fetal pituitary from very early in gestation (50 days), and there is no evidence for a larger molecular weight form, as seen in the immature human fetus.
Journal of Endocrinology (1991) 129, 335–341
Search for other papers by L. R. Altschuler in
Google Scholar
PubMed
Search for other papers by J. A. Ceppi in
Google Scholar
PubMed
Search for other papers by M. N. Ritta in
Google Scholar
PubMed
Search for other papers by R. S. Calandra in
Google Scholar
PubMed
Search for other papers by A. A. Zaninovich in
Google Scholar
PubMed
ABSTRACT
The effects of thyroxine (T4) were studied on the concentration of oestrogen receptors in the anterior pituitary gland and hypothalamus of ovariectomized euthyroid and hypothyroid rats. A group of rats was made hypothyroid by the administration of I. Seven days after ovariectomy, animals were separated into five groups: I, euthyroid controls; II, hypothyroid controls; III, hypothyroid and injected with oestradiol benzoate (10 μg/day for 10 days); IV, hypothyroid and injected with T4 (4 μg/day for 10 days) and V, hypothyroid and injected with both oestradiol and T4 as described above. In group I, oestrogen receptor levels in pituitary cytosol were 44·4 ± 3·4 (s.d.) fmol/mg protein and in the nucleus 47·7 ± 4·0 fmol/mg DNA. In group II the respective values were 12·8 ± 1·7 fmol/mg protein (P <0·01) and 12·7 ± 1·7 fmol/mg DNA (P <0·01 compared with group I). In group III, cytosolic receptor concentrations decreased when compared with those in group II (P <0·05), whereas nuclear receptor concentrations rose significantly (P <0·01). Group IV had both pituitary cytosolic and nuclear receptors increased (P <0·01 compared with group II). In group V there were no changes in cytosolic receptor concentrations but a significant (P <0·01) rise in nuclear receptors as compared with group II. Hypothalamic oestrogen receptors in untreated hypothyroid rats (group II) were unchanged in the cytosol and diminished (P <0·01) in the nucleus in relation to euthyroid controls (group I). Thyroxine, but not oestrogen, was effective in increasing the concentration of cytosolic receptors (P <0·05). Neither hormone caused changes in nuclei. The results show that there is a pronounced decrease in pituitary and hypothalamic (nuclei) oestrogen receptors in untreated hypothyroid rats and that this decrease can be reversed by T4 treatment.
J. Endocr. (1988) 119, 383–387
