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Biomedical subjects

H M Fraser

Publications and source records attributed to H M Fraser.

At least 145 records · Page 8Linked to original sources
PubMed1983

Specific binding of luteinizing hormone releasing hormone to human luteal tissue.

Homogenates of human luteal tissue bound radioiodinated luteinizing hormone releasing hormone agonist. Specific binding was both time- and temperature-dependent. Native LHRH and two LHRH agonists competed for binding, whereas TRH, somatostatin and oxytocin did not, indicating that the binding sites were specific. The apparent Ka values were 2 X 10(7)M-1 for both LHRH agonists and 10(6)M-1 for native LHRH. This is the first demonstration of specific binding of LHRH to human ovarian tissue. No binding could be detected to ovarian tissue from postmenopausal women.

Binding, Competitive↗
PubMed1983

beta-Endorphin regulates lordosis in female rats by modulating LH-RH release.

Several lines of evidence have implicated the endogenous opioid peptides in the regulation of masculine sexual behaviour. However, although the opioid related peptides alpha-melanocyte stimulating hormone (alpha-MSH) and adrenocorticotropin (ACTH) have been shown to affect lordosis behaviour in the female rat, there is as yet no evidence for a role of the endogenous opiates in the regulation of female sexual behaviour. We present here evidence that the endogenous opiates in the mesencephalic central grey (MCG) are involved in the control of lordosis behaviour in the female rat.

Animals↗
PubMed1983

Active immunization of stumptailed macaque monkeys against luteinizing hormone releasing hormone, and its effects on menstrual cycles, ovarian steroids and positive feedback.

Five female stumptailed macaque monkeys with regular menstrual cycles were immunized against luteinizing hormone releasing hormone (LHRH) conjugated to tetanus toxoid. The conjugate was given in Freund's complete adjuvant (3 monkeys) or dipeptide adjuvant (2 monkeys). Only the 3 monkeys immunized using Freund's adjuvant produced LHRH antibody titres capable of having effects on menstrual cycles. Elevated levels of LHRH antibody were associated with an absence of preovulatory luteinizing hormone (LH) surges in serum and an inability to respond to an injection of oestradiol benzoate which produced an LH surge (positive feedback) in control animals. Cyclical rises in serum concentrations of follicle-stimulating hormone (FH) were also abolished when LHRH antibody levels were elevated. These effects on LH and FSH caused a reduction in serum concentrations of 17 beta-oestradiol and absence of progesterone rises indicating inhibition of follicular development and ovulation, which resulted in amenorrhoea. Time to decline of LHRH antibody titres leading to re-establishment of menstrual cycles varied but could be reversed by booster immunizations.

Animals↗
PubMed1983

The role of LH in regulation of Leydig cell responsiveness to an LHRH agonist.

The short-term relationship between deprivation of LH and changes in the responsiveness of isolated Leydig cells to an LHRH agonist was studied in adult rats injected with a potent antiserum to oLH. This treatment suppressed serum and intra-testicular levels of testosterone within 4 h of injection by 80-90% and 70%, respectively, with further suppression to levels found in hypophysectomized rats by 20 h. At 12-20 h after antiserum injection there was no major consistent change from control values in the number of Leydig cell LH (hCG)-receptors or in the testosterone response of the cells to hCG-stimulation. In the same cells the number of LHRH-receptors and the maximal testosterone response to LHRH agonist were increased (P less than 0.001) by 50% or more, although the magnitude of increase varied considerably between experiments. The ability of LHRH agonist to enhance the testosterone response of cells to hCG-stimulation was also increased significantly (P less than 0.001) in antiserum-treated rats. Comparable changes in testosterone responsiveness to LHRH agonist were observed following purification of Leydig cells on Percoll gradients. Although there was some evidence for changes in Leydig cell LHRH-receptor numbers and responsiveness to LHRH agonist at 4 h after intravenous antiserum injection, these changes were small compared with changes seen at later times. It is concluded that Leydig cell responsiveness to an LHRH agonist is negatively regulated by LH, and this has implications with respect to a possible role of 'testicular LHRH' in regulation of the intra-testicular levels of testosterone.

Animals↗
PubMed1983

Stimulation of androstenedione and progesterone release by LHRH and LHRH agonist from isolated rat preovulatory follicles.

Incubation of preovulatory rat follicles isolated from PMSG-treated immature rats for periods of less than 24 h in the presence of LHRH or LHRH agonist resulted in stimulation of basal androstenedione and progesterone release. The stimulatory effects seen were time-dependent, occurring from 2-3 h for androstenedione and from 8-20 h incubation for progesterone. Dose-dependent stimulation occurred with both LHRH agonist (in the range 5 X 10(-10) to 10(-8) M) and native LHRH (from 10(-9) to 10(-6) M), both being in the range of the reported Ka for ovarian LHRH receptors. LHRH did not enhance the stimulatory effect of 1-100 mIU hCG on androstenedione and progesterone release. These results show for the first time that LHRH and LHRH agonist can exert a stimulatory action on androgen release from isolated preovulatory follicles. This suggests that LHRH may be acting either directly at the thecal cell level or indirectly via decreased granulosa cell aromatization.

Androstenedione↗
PubMed1983

Control of pulsatile LH release in male rats.

Distinct, short-term pulses of pituitary luteinizing hormone (LH) release are a characteristic feature of tonic LH secretion in normal rats. LH pulses are more pronounced, more frequent, and more regular in castrated rats. Using castrated rats, we sought to identify the basis of the pulsatile discharge of LH by the pituitary gland. Indwelling atrial cannulae were used to obtain frequent blood samples through 3-4 h from three cohorts of conscious, freely moving, orchidectomized male rats. Rats were (1) untreated castrates, (2) infused with ovine antiserum to LHRH or control serum, or (3) infused with a luteinizing hormone releasing hormone (LH-RH) analog, [D-pGlu1,D-Phe2, D-Trp3,6]-LH-RH. Castrates exhibited a pulsatile pattern of circulating LH levels; the mean (+/- SE) peak level of LH pulses was 640 +/- 15 ng/ml, with a mean (+/- SE) pulse period of 18.5 +/- 0.8 min. LH-RH antiserum arrested pulsatile LH secretion immediately, leaving plasma LH levels at 80-120 ng/ml. The LH-RH analog caused a similar suppression of LH release, although this effect was of a shorter duration than the suppression of LH pulses induced by LH-RH antiserum. The obliteration of LH pulses by anti-LH-RH and suppression of LH release by an LH-RH antagonist indicate that the pulsatile secretion of LH is due to corresponding stimulation of the pituitary gland by hypothalamic LH-RH. Anti-LH-RH and an LH-RH antagonist are identified as valuable probes for the experimental dissection of blood-borne signals within the rat hypothalamic-pituitary-testicular axis.

Animals↗
PubMed1983

Increased sensitivity to the negative feedback effects of testosterone induced by hyperprolactinemia in the adult male rat.

High plasma levels of PRL induced by transplants of two donor pituitaries under the kidney capsule of adult male rats resulted in a prolonged suppression of plasma levels of LH and FSH although testosterone levels were maintained within normal limits. Castration of rats with pituitary transplants resulted in a normal though delayed rise in serum levels of both LH and FSH to levels equivalent to those in normal castrated controls. This increase in gonadotropin levels occurred in spite of maintenance of elevated PRL levels. Two experiments were carried out in which testosterone was restored after castration by Silastic testosterone-containing implants of various lengths (Exp 1:60, 30, and 10 mm; Exp 2: 30, 20, 10, 5, and 2 mm). In both experiments 60- and 30-mm testosterone implants prevented the postcastration rise in LH and FSH in both control and hyperprolactinemic rats. However, although the shorter testosterone implants delayed this rise in control rats, levels of LH and FSH increased by 4 days and were not significantly different from castrated rats without testosterone implants by 15 days after castration. In contrast, this rise in gonadotropins was abolished or considerably delayed by the shorter implants in hyperprolactinemic rats, demonstrating an increase in sensitivity of the hypothalamic pituitary axis to the negative feedback effects of testosterone in these animals. These results suggest that 1) to maintain suppression of gonadotropin secretion in hyperprolactinemia high levels of PRL alone are insufficient and gonadal steroids are required, and 2) high levels of PRL appear to sensitize the hypothalamic-pituitary axis to the negative feedback effects of gonadal steroids.

Animals↗
PubMed1983

Thyrotropin-releasing hormone in rat pituitary stalk blood and hypothalamus: studies with high performance liquid chromatography.

Immunoreactive TRH (TRH-IR) in rat pituitary stalk blood and hypothalamus was investigated with high performance liquid chromatography in conjunction with a sensitive RIA. The TRH-IR of ethanol extracts of stalk blood resolved into three peaks, whether the blood was collected with the pituitary gland in situ or after the gland had been removed. The first peak corresponded to authentic TRH. By contrast, all the immunoreactive TRH in pituitary and hypothalamic extracts and in peripheral blood to which hypothalamic or synthetic TRH had been added eluted as a single peak with the same retention time as authentic TRH. The additional IR peaks in stalk blood did not correspond to known metabolites of TRH, and, since absent from the hypothalamus, they are unlikely to represent stored TRH precursors. Although authentic TRH constituted only 37% of total TRH-IR in pituitary stalk blood, the amount released during the first hour into stalk blood (1.7 ng) in relation to hypothalamic content (approximately 5 ng) was still high (approximately 34%) compared with that of LHRH (approximately 0.6%) and somatostatin (approximately 0.3%).

Animals↗
PubMed1983

Antibody production against an agonist analogue of luteinizing hormone-releasing hormone: evaluation of immunochemical and physiological consequences.

Because of the widespread long-term clinical use of luteinizing hormone-releasing hormone (LRH) agonists, the possibility of antibody development to one of these, (D-Ser-(Butt)6) LRH (1-9) nonapeptide-ethylamide (buserelin), has been studied by examining sera from experimental animals and humans receiving long-term agonist-treatment for ability to bind 125I-labelled buserelin. None of the sera from monkeys, rabbits, dogs or rats receiving buserelin by sc injection or via minipump or from 81 patients receiving the agonist by sc injection or nasal spray had detectable antibodies. The immunochemistry of buserelin was investigated by actively immunizing male rabbits against the agonist. This also enabled us to determine the possibility of this stimulus to the immune response resulting in the generation of antibodies which could cross-react with endogenous LRH and neutralize its biological effect. All 41 rabbits immunized against unconjugated buserelin and all 23 immunized against buserelin conjugated to a protein carrier developed antibodies, those in the latter group producing highest titres. Serum from one of the animals immunized against unconjugated buserelin and from 9 of the animals immunized against conjugated buserelin had the capacity to bind 125I-labelled LRH. These LRH antibody titres were very low and were insufficient to cause suppression of serum testosterone concentrations or affect testicular weight except in one rabbit immunized against unconjugated agonist. The LRH antibody titre in this rabbit was always less than 1:100 which our other studies have indicated to be too low to produce a biological effect. It may be that the association of low LRH antibody titre with decreased testes weight in this animal was fortuitous. We conclude that the possibility of circulating antibodies being produced to buserelin or their interfering with the action of endogenous LRH is extremely low.

Animals↗
PubMed1983

Effects of LH-RH agonist or LH-RH immunoneutralization on pituitary and ovarian LH-RH receptors in female rats.

Hyperstimulation of pituitary function using daily injections of 50,500 or 5000 ng LH-RH agonist for 3 weeks or hypostimulation by immunoneutralization of endogenous LH-RH led to disrupted oestrous cycles and profound changes in ovarian morphology. Despite this, the number of pituitary and ovarian LH-RH receptors remained within the range found in normally cyclic animals. Autoradiography confirmed that specific binding was located in theca, granulosa and luteal cells. These results suggest that autoregulation of pituitary and ovarian LH-RH receptors is not of primary importance in the cyclic female rat.

Animals↗
PubMed1983

Differential effects of LH-RH immunoneutralization on LH and FSH secretion in the ewe.

Neutralization of LH-RH by injection of an ovine antiserum to LH-RH in ewes during the late follicular phase of the oestrous cycle resulted in an immediate blockade of pulsatile secretion of LH. Plasma concentrations of FSH gradually rose in the antiserum-treated ewes during the 36-h study period but levels declined in control ewes. These results show that, in the ewe, pulsatile LH secretion is dependent on LH-RH from the hypothalamus, while FSH is largely unresponsive to short-term reduction of LH-RH stimulation. Since reduction in LH secretion is likely to reduce ovarian function, the changes in FSH secretion may be attributed to the removal of a negative feedback influence of an ovarian factor, perhaps oestradiol, on FSH secretion.

Animals↗
PubMed1982

Effect of immunological castration on sexual and production characteristics in male cattle.

Ten male Friesian calves were actively immunised against luteinising hormone releasing hormone and their production compared with 10 Friesian steer calves. Five of the immunised calves responded poorly (group 1); the other five responded well (group 2), resulting in high antibody titres, low serum testosterone levels, involuted testes, reduced libido and semen production, and docile behavior. The castration effect lasted approximately six months before reversion to near normal male status. This temporary immunocastration failed to affect seriously performance until slaughter, and liveweight gain was substantially better in this group than in the steers. Carcase traits were similar in groups 1 and 2, but the lean content in both was considerably greater than in the steer carcases.

Animals↗