Search Results
You are looking at 1 - 10 of 13 items for
- Author: H. M. Charlton x
- Refine by access: All content x
Search for other papers by G. Fink in
Google Scholar
PubMed
Search for other papers by W. J. Sheward in
Google Scholar
PubMed
Search for other papers by H. M. Charlton in
Google Scholar
PubMed
We have investigated the LH response to LH releasing hormone (LH-RH) in female hypogonadal (hpg) mice in which the hypothalamus contains no LH-RH and the pituitary gland contains significantly less LH than in normal mice. Both the releasing action and the priming effect of LH-RH were not significantly different in hpg compared with normal mice. Raised plasma concentrations of oestradiol-17β reduced pituitary responsiveness to LH-RH in normal but not in hpg mice. These results show that in the mouse neither longterm exposure to normal levels of LH-RH nor a normal pituitary content of LH are necessary for either the releasing or the priming action of LH-RH.
Search for other papers by CAROL A. IDDON in
Google Scholar
PubMed
Search for other papers by H. M. CHARLTON in
Google Scholar
PubMed
Search for other papers by G. FINK in
Google Scholar
PubMed
SUMMARY
Electrical stimulation of the median eminence, using parameters known to cause the release of LH in normal male mice, failed to elicit any gonadotrophin response in hypogonadal (hpg) male mice. Administration of 40 ng synthetic LH releasing hormone (LH-RH) resulted in release of LH from the pituitary gland of hpg mice, although the response was significantly lower than that of normal mice. These results were consistent with the hypothesis that the hypogonadal state of the hpg mouse results from a functional absence of LH-RH in the hypothalamus rather than from a lack of response of the pituitary gland to the releasing hormone.
Search for other papers by I. F. W. McDowell in
Google Scholar
PubMed
Search for other papers by J. F. Morris in
Google Scholar
PubMed
Search for other papers by H. M. Charlton in
Google Scholar
PubMed
Hypogonadal (hpg) mice lack hypothalamic luteinizing hormone releasing hormone (LH-RH). Gonadotrophs from male hpg mice have been identified by immunocytochemistry for LH and quantitative electron microscopy allied with radioimmunoassay of the gonadotrophins. In comparison with those of normal mice, gonadotrophs in male hpg animals are less numerous and smaller, with less cytoplasm and rough endoplasmic reticulum and a smaller Golgi apparatus. They have fewer granules, especially those of larger (> 210 nm) diameter. Thus, in the absence of LH-RH, gonadotrophs can differentiate but remain relatively inactive.
Search for other papers by H. D. Nicholson in
Google Scholar
PubMed
Search for other papers by R. T. S. Worley in
Google Scholar
PubMed
Search for other papers by H. M. Charlton in
Google Scholar
PubMed
Search for other papers by B. T. Pickering in
Google Scholar
PubMed
ABSTRACT
Immunoreactive oxytocin is present in the testis and it has been shown that this hormone increases the contractility of seminiferous tubules. We have investigated the relationship between testicular oxytocin, tubular movements and the effects of LH and testosterone using, as a model, the hypogonadal (hpg/hpg) mouse, which is deficient in hypothalamic LH-releasing hormone (LHRH). Whilst both testicular oxytocin and seminiferous tubule movements, resembling those seen in the rat, can be found in normal adult mice, neither can be found in hypogonadal mice. After 2 weeks of treatment with LH (200 ng to 100 μg daily) low levels of testicular oxytocin and tubular movements were observed. Treatment with large doses of testosterone for 2–12 weeks led to higher concentrations of testicular oxytocin and tubular movements resembling those seen in the normal adult mouse. The results support the evidence that testicular oxytocin modulates seminiferous tubule movements. We suggest that testosterone may play a part in the accumulation of oxytocin in the testis.
J. Endocr. (1986) 110, 159–167
Search for other papers by J. M. S. Bartlett in
Google Scholar
PubMed
Search for other papers by H. M. Charlton in
Google Scholar
PubMed
Search for other papers by I. C. A. F. Robinson in
Google Scholar
PubMed
Search for other papers by E. Nieschlag in
Google Scholar
PubMed
ABSTRACT
The pubertal development of a novel GH-deficient mutant, the dwarf rat, has been evaluated. The establishment of normal spermatogenic function within small testes suggests that GH plays no role in spermatogenic function during puberty and adult life. However, a reduction in testicular size may reflect a reduced Sertoli cell population, suggesting that GH may be of importance in prepubertal testicular development.
Furthermore, marked differences between the homozygous dwarf rat and homozygous GH-deficient mouse mutants (e.g. Snell, Ames, pygmy and little mutants) have been demonstrated. It would appear that the GH deficiency in the rat mutant is far more specific for GH than those hitherto described in the mouse. In contrast to Snell dwarf mice mutants, pituitary and serum concentrations of FSH and LH are normal throughout pubertal development in the dwarf rat. Both spermatogenic function and seminal vesicle function develop normally, whilst in Snell dwarf mice spermatogenic function develops late in life and seminal vesicles remain infantile. Serum and testicular concentrations of androgen are also normal in dwarf rats. Homozygous dwarf rats have been shown to be fertile in previous studies; however, our observations suggest that despite spermatogenesis being qualitatively and quantitatively normal when assessed histologically, reduced testicular size seen in dwarf rats would lead to a reduced daily sperm output in these animals.
The dwarf rat represents a mutant in which the consequences of the selective depletion of GH may be studied on various endocrine systems. The reproductive axis appears to be only partially affected, at an early age, by GH deficiency.
Journal of Endocrinology (1990) 126, 193–201
Search for other papers by H. M. Charlton in
Google Scholar
PubMed
Search for other papers by Dilys Parry in
Google Scholar
PubMed
Search for other papers by D. M. G. Halpin in
Google Scholar
PubMed
Search for other papers by R. Webb in
Google Scholar
PubMed
Hypogonadal mice are deficient in LH releasing hormone (LH-RH), the releasing factor for LH and FSH, with a consequent failure of postnatal ovarian and testicular development. After intravenous injection of hypogonadal females with 125I-labelled human chorionic gonadotrophin (hCG), followed by autoradiography of semi-thin (1 μm) slices of the ovary, labelled hCG was found to be associated with interstitial cells and thecal cells with little or no labelling of granulosa cells. Labelled human FSH was associated solely with granulosa cells. Hypogonadal females, implanted for 5 days with a silicone elastomer capsule of oestrogen, showed a similar response to that of normal females with hCG labelling of the granulosa cells of the larger follicles as well as of the thecal cell layer. Furthermore, subcutaneous injection of hypogonadal females with LH-RH (50 ng), 12 times daily for 5 days, increased uterine weight and stimulated ovarian development with some large follicles binding hCG to both thecal and granulosa cells. Therefore stimulation of follicular development may possibly be associated with increased oestradiol concentrations.
In the male, after injection of 125I-labelled hCG, silver grains were associated with the interstitial cells alone in both hypogonadal and normal mice. Labelled human FSH was undetectable in semi-thin testicular sections, but the mode of injection (intravenous) may not have allowed enough labelled hormone to reach the testis in order to resolve the question as to whether the hypogonadal or normal testis can bind FSH.
Search for other papers by P. J. O'Shaughnessy in
Google Scholar
PubMed
Search for other papers by M. K. Bennett in
Google Scholar
PubMed
Search for other papers by I. S. Scott in
Google Scholar
PubMed
Search for other papers by H. M. Charlton in
Google Scholar
PubMed
ABSTRACT
The hypogonadal (hpg) mouse has a congenital deficiency in gonadotrophin-releasing hormone and the gonads consequently lack exposure to endogenous gonadotrophins during development. To determine the effect of FSH on Leydig cell function in these animals adult hpg mice were injected twice daily with FSH (2 μg injections) or LH (40 ng injections, the presumed LH contamination of FSH used). Following FSH treatment there was a clear stimulation of the seminiferous epithelium and in animals injected with FSH plus [3H]thymidine, the incorporation of label was largely confined to the germ cells with no apparent uptake by the Sertoli cells. In FSH-treated testes the Leydig cells contained numerous large lipid droplets, similar to the unstimulated hpg testis. There was no evidence of the interstitial hyperplasia which is observed following injection of high doses of LH (2 pg twice daily).
There was no change in basal androgen content of the testis in vivo following FSH treatment but injection of a maximal dose of human chorionic gonadotrophin (hCG), 1 h before death, markedly increased testicular androgen content only in the FSH-treated group. Testicular androgen production in vitro was significantly increased following FSH treatment both under basal conditions (FSH-treated, 17·4 pmol/testis; control, 1·46 pmol/testis) and during stimulation by hCG (FSH-treated, 940 pmol/testis; control, 81 pmol/testis). Associated with the increased androgen production following FSH treatment there were significant increases in the activities of three steroidogenic enzymes; cholesterol side-chain cleavage (186-fold increase over control), 17α-hydroxylase (103-fold increase) and 17-ketosteroid reductase (177-fold increase). The fourth enzyme involved in androgen synthesis, 3β-hydroxysteroid dehydrogenase, shows relatively high activity in the control hpg testis and was only increased by sixfold following FSH treatment. There was no effect of FSH on 5α-reductase activity.
Results show that FSH causes a marked stimulation of the steroidogenic capacity of the hpg testis. Leydig cells do not contain FSH receptors and it is assumed that FSH acts through paracrine factors released by the Sertoli cells.
Journal of Endocrinology (1992) 135, 517–525
Search for other papers by C. E. Lewis in
Google Scholar
PubMed
Search for other papers by A. Megson in
Google Scholar
PubMed
Search for other papers by J. F. Morris in
Google Scholar
PubMed
Search for other papers by H. M. Charlton in
Google Scholar
PubMed
ABSTRACT
We have investigated the effects of multiple 2-hourly injections of LH-releasing hormone (LHRH) on the number and size of the gonadotrophs and gonadotroph secretory granules, and the lipid content of gonadotrophs in the pituitary glands of intact and gonadectomized male and female hypogonadal (hpg) mice. Gonadotrophs were identified by immunocytochemistry for LHβ, and the size and secretory status of the gonadotrophs were assessed by quantitative ultrastructural analysis of immunoidentified gonadotrophs. The administration of 60 ng LHRH by subcutaneous injection every 2 h for 15 days resulted in an increase in the number, size and granule content of LHβ-immunoidentified gonadotrophs of hpg mice to values found in normal adult mice. Large lipid droplets accumulated in 30–40% of the gonadotrophs in both male and female LHRH-treated hpg mice. Although lipid-containing gonadotrophs were larger than lipid-free cells in all LHRH-treated groups irrespective of the presence or absence of gonads, a marked difference in the number, position within the cell, and size of the secretory granules between the lipid-containing and lipid-free cells was found only in the pituitary glands of intact LHRH-treated hpg females.
These results demonstrate: (a) that the effects of multiple injections of LHRH on the morphology of the gonadotrophs of hpg mice is not dependent on the presence of functioning gonads, although ovarian factors are required for the full development of morphological, and hence possibly functional, heterogeneity in the gonadotroph population in female animals, and (b) that, although multiple injections of LHRH in hpg mice are more effective than single daily injections of LHRH in stimulating pituitary-gonadal function, there is no obvious difference in the morphologically recognizable effects that these two modes of administration have on the pituitary gonadotrophs.
J. Endocr. (1986) 111, 483–493
Search for other papers by C. M. Faull in
Google Scholar
PubMed
Search for other papers by J. A. Charlton in
Google Scholar
PubMed
Search for other papers by T. J. Butler in
Google Scholar
PubMed
Search for other papers by P. H. Baylis in
Google Scholar
PubMed
ABSTRACT
To explore the hypothesis that serotonin (5-HT) is important in osmoregulated arginine vasopressin (AVP) secretion, we administered (i.p.) fluoxetine (FL) a 5-HT reuptake inhibitor (10 mg/kg body weight), ritanserin (RIT), an antagonist at the 5-HT2 and 5-HT1c receptor subtypes (1 mg/kg body weight), 1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride (DOI), a 5-HT2 receptor agonist (1 mg/kg body weight) or vehicle to rats 30 min before they were given an osmotic challenge. Rats received distilled water, normotonic saline (150 mmol NaCl/l) or hypertonic saline (500 mmol NaCl/l) (20 ml/kg i.p) and were killed 30 min later. The osmotic stimulus alone produced significant (P<0·001) effects on plasma osmolality and plasma sodium but FL, RIT and DOI did not have any significant effect on this stimulus. FL had no significant effect on the osmotic threshold of AVP release but significantly (P<0·001) increased basal AVP secretion from 1·6 ± 1·0 to 3·1 ± 1·3 (s.e.m.) pmol AVP/l and significantly (P<0·001) increased the AVP response to changes in plasma osmolality: vehicle-treated, 0·7 ± 0·4; FL-treated, 1·7 ± 0·2 pmol AVP/l per mOsm per kg. Neither RIT nor DOI had any significant effect on basal or stimulated AVP secretion. In a second study, RIT was administered 60 min i.p. prior to FL i.p. (doses as above), which was followed 30 min later by a hypertonic stimulus i.p. and rats were killed 30 min after hypertonic saline treatment. RIT had no significant effect on the AVP response to plasma osmolality and did not significantly alter the FL-augmented AVP response, suggesting that neither the 5-HT2 nor the 5-HT1c receptors are involved in the response of AVP to FL. We conclude that FL modulates osmoregulated AVP secretion but that the mechanism of this is unknown and is apparently not through the 5-HT2 or 5-HT1c receptor subtypes.
Journal of Endocrinology (1993) 139, 77–87
Search for other papers by J. A. Charlton in
Google Scholar
PubMed
Search for other papers by C. J. Thompson in
Google Scholar
PubMed
Search for other papers by J. M. Palmer in
Google Scholar
PubMed
Search for other papers by S. Thornton in
Google Scholar
PubMed
Search for other papers by P. H. Baylis in
Google Scholar
PubMed
ABSTRACT
To investigate whether hyperglycaemic ketoacidotic diabetic rats continue to osmoregulate the secretion of arginine vasopressin (AVP), male Wistar rats were injected with streptozotocin (150 mg/kg body weight). Rats rendered diabetic were maintained on protamine–zinc insulin (PZI) for 11 days (insulin-treated rats; n = 35), after which PZI was withdrawn for 72 h in half the rats (insulin-withdrawn rats). Insulin-withdrawn and -treated rats were divided into two groups; one was injected i.p. with distilled water (20 ml/kg) and the other with hypertonic saline (500 mmol NaCl/l; 20 ml/kg), and killed 30 min after injection. Insulin-withdrawn rats (water loaded and osmotically stimulated) were hyperglycaemic (16·5 ± 0·8 and 16·5 ± 0·9 mmol glucose/l respectively) and ketotic (2077 ± 664 and 1474 ± 170 μmol acetoacetate/l respectively). Insulin-treated rats were euglycaemic and non-ketotic. Osmotic manipulation caused similar changes in plasma sodium in both insulin-withdrawn and -treated rats. Plasma AVP was low in the water-loaded rats (0·6 ± 0·1 and 4·5 ± 0·9 pmol/l in the insulin-treated and -withdrawn rats respectively) and increased in rats injected with hypertonic saline (1·2 ± 1·8 and 35·2 ± 17·9 pmol/l respectively). There was no evidence of hypotension and hypovolaemia in any group of rats. Linear regression analysis defined the functions: plasma AVP = 2·56 (plasma Na – 141), r = +0·63, P < 0·01 for hyperglycaemic ketotic rats; plasma AVP = 0·83 (plasma Na – 146), r = +0·78, P < 0·001 for insulin-treated animals. The slopes and abscissal intercepts were significantly (P < 0·05) different. We conclude that the hyperglycaemic ketotic diabetic rat retains the ability to osmoregulate AVP secretion.
Journal of Endocrinology (1989) 123, 413–419
