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Biomedical subjects

H M Fraser

Publications and source records attributed to H M Fraser.

At least 163 records · Page 9Linked to original sources
PubMed1982

The secretion, measurement, and function of a testicular LHRH-like factor.

In this paper we have demonstrated the presence and secretion within the testis of a factor that is immunologically distinct from LHRH, but that has receptor-binding and bioactive features similar to LHRH. The major source of this LHRH-like factor is probably the Sertoli cell and, as its site of action appears to be restricted to the Leydig cells, it is possible that it is one of the means by which the Sertoli cell has been postulated to regulate the Leydig cell. All of the available evidence suggests that the action of the LHRH-like factor on the Leydig cell is inhibitory, and it may mediate some or all of the negative effects on the Leydig cell of LH and hCG. The precise role of the LHRH-like factor, particularly under physiological conditions (i.e., low level stimulation with LH), remains to be determined, but the availability of methods for its extraction, measurement, and inactivation should enable this problem to be resolved within the near future. Moreover, the recognition that Leydig cell function may be regulated by local factors within the testis should open up new avenues of research that may lead to improved methods for the regulation of fertility in the male.

Aging↗
PubMed1982

Effect of passive immunization against LH-RH on gonadotropin secretion in the ferret.

Administration of ovine antiserum containing antibodies against synthetic LH-RH to spayed female ferrets caused an immediate fall in plasma LH concentration and by 2 h after injection circulating levels had declined by 70--80%. A further decline of 50% was observed on Day 2, but by Day 4 a return to normal levels had begun and control values were regained on Day 6. In contrast, the fall in plasma FSH concentration was delayed, with a significant reduction being first observed on Day 2 and minimal values occurring on Day 4. Control values were regained by Day 7. The results accord with the concept that a single hypothalamic releasing factor controls the tonic secretion of both pituitary hormones. However, the slow change in FSH secretion implies that the mechanism for FSH release may be more autonomous than that for LH.

Animals↗
PubMed1982

Antler growth in male red deer (Cervus elaphus) after active immunization against LH-RH.

Four sexually mature male red deer were actively immunized against LHRH and this caused 3 of the animals to cast their antlers prematurely in the autumn instead of the spring. Development of new antlers was initiated after casting, but the effects on the antler cycle were variable and correlated with the antibody titre, only the animal with the highest titre developed antlers that resembled those of a castrate and remained 'in velvet' for more than 6 months. In October, when all the immunized deer had peak circulating levels of LHRH antibodies, the testes were reduced in size compared to the maximum values of the controls. The blood levels of testosterone were reduced in the immunized animals, and there was a minimal increase in the circulating levels of testosterone in response to an i.v. injection of 100 micrograms ovine LH. The immunized stags showed no rutting behaviour in the autumn. The changes in the testes confirm that the immunizations were effective in blocking the secretion of the gonadotrophic hormones. The re-development of antlers in these animals indicates that gonadotrophins are not directly involved in stimulating antler growth.

Animals↗
PubMed1981

Sertoli-Leydig cell communication via an LHRH-like factor.

The primary function of the testosterone secreted by Leydig cells is the maintenance of spermatogenesis and hence fertility. This action of testosterone is mediated by the Sertoli cells which nourish and support the developing spermatozoa. As normal Sertoli cell function is so critically dependent on normal Leydig cell function, a regulatory influence of the Sertoli cells on the Leydig cells has been suggested. Indeed, follicle-stimulating hormone (FSH), which acts only on Sertoli cells, can also cause profound changes in Leydig cell function, although how this is effected is unknown. We recently hypothesized that the Sertoli cell might be the source of a luteinizing hormone releasing hormone (LHRH)-like factor which we detected in the interstitial fluid surrounding the Leydig cells. As injected LHRH agonists cause impairment of gonadal function and directly inhibit FSH-induced changes in Leydig cell function through specific membrane receptors, this 'LHRH-like' factor has all the correct credentials for the postulated messenger between the Sertoli and Leydig cells. Here, we strengthen this case by demonstrating that seminiferous tubules from both the rat and the stumptailed macaque (Macaca arctoides) contain a factor which has LHRH-like receptor-binding and biological activity in vitro, but which is immunologically distinct from native LHRH. We have also shown that this factor is secreted in vitro by cultured rat Sertoli cells.

Animals↗
PubMed1981

Effects of chronic LHRH agonist treatment on the endometrium and ovaries of the stumptailed macaque.

Eight stumptailed macaques were injected daily with 5 or 20 micrograms D-Ser(But)6des Gly luteinizing hormone releasing hormone ethylamide (LHRH agonist) for approximately one year in order to prevent ovulation. On the last day of treatment (7 monkeys) or during the mid-luteal phase of the first cycle after treatment (1 monkey), a laparotomy was performed. Uterine size was slightly smaller (P less than 0.01) than in controls with normal cycles (n = 6). A full thickness wedge of anterior uterine wall was excised and examined histologically. Five of the agonist-treated monkeys had endometrium consistent with an atropic or resting proliferative pattern, but in 2 the appearance varied from early proliferative to marked secretory. All appeared entirely benign. The remaining animal studied in the luteal phase after stopping treatment exhibited a normal secretory endometrium. Ovaries from 2 of the LHRH agonist-treated animals were also studied histologically and found to consist of follicles at various stages of maturation. The occurrence of endometrial activity in 2 of the 8 LHRH agonist-treated monkeys stresses the need for careful endometrial assessment during clinical trials involving repeated administration of LHRH agonists in women.

Animals↗
PubMed1981

Effect of oestrogen and an LH-RH agonist on the release of gonadotrophins in ovariectomized ewes deprived of LH-RH.

Endogenous LH-RH in ewes was inhibited by active immunization or by injection of LH-RH antiserum. Plasma levels of LH and FSH were elevated in 3 ovariectomized control ewes but low in 3 LH-RH immunized ovariectomized ewes. Oestradiol benzoate (50 microgram i.m.) caused a marked rise in LH concentrations in control ewes but not in the immunized ewes. In the immunized ewes the low plasma levels of FSH decreased even further 8-36 h after injection of oestrogen, indicating a direct inhibitory action of the steroid on the pituitary. Both groups responded to the oestrogen injection by a rise in plasma levels of prolactin and by exhibiting normal oestrous behaviour. When the control ewes were again challenged with oestradiol benzoate and, after 10 h, given an i.v. injection of 75 ml antiserum to LH-RH, the LH surge was abolished in one animal and reduced in another. These experiments indicate that the continued presence of LH-RH is necessary for the occurrence of the oestrogen-induced LH surge in the ewe. Administration of a stimulatory analogue of LH-RH released LH and FSH in control and immunized ewes but the responsiveness to further injections at intervals of 3 h decreased, particularly for FSH.

Animals↗
PubMed1981

Inadequate corpus luteum function after the induction of ovulation in anoestrous ewes by LH-RH or an LH-RH agonist.

Scottish Blackface ewes were given LH-RH (3 x 30 micrograms i.v., at 90 min intervals) or D-Ser-(But)6-des Gly10 LH-Rh ethylamide (LH-RH agonist) as a single injection (8 or 40 micrograms) during anoestrus. Ovulation as judged by laparoscopy occurred in 8 of the 27 animals. Despite the fact that the LH-RH agonist induced a greater release of LH and FSH the different treatments had no effect on the number of ewes ovulating and within each treatment group there was no apparent difference in the amounts of gonadotrophins released between the ewes that did or did not ovulate. All ovulations resulted in the formation of CL associated with plasma progesterone concentrations of less than 1 ng/ml (1--5 ng/ml in the normal luteal phase). In comparison with CL of the normal cycle the induced CL were of lower weight and had reduced progesterone content and ability to secrete progesterone in vitro. However, the binding of hCG was equivalent to that of normal CL. These results suggest that the inadequate CL formed in anoestrous ewes after a single LH-RH injection have not developed the ability to synthesize and secrete progesterone in spite of the presence of normal amounts of LH receptors.

Animals↗
PubMed1981

Effect of oestrogen on gonadotrophin release in stumptailed monkeys (Macaca arctoides) treated chronically with an agonist analogue of luteinizing hormone releasing hormone.

Nine adult female stumptailed monkeys (Macaca arctoides) treated chronically with daily s.c. injections of D-Ser(But)6,des-Gly10,Proethylamide9, luteinizing hormone releasing hormone (LH-RH agonist) to inhibit ovulation, were tested for their ability to respond to an oestrogen provocation test (positive feedback). On two occasions during treatment with the LH-RH agonist (first test between 10 and 35 weeks after treatment had started; second test between 30 and 60 weeks after) the animals were given an i.m. injection of 50 micrograms oestradiol benzoate/kg in arachis oil. Controls were tested between days 1 and 5 of the normal cycle. In the control monkeys oestrogen induced a clear rise in LH and FSH concentrations in the blood, with highest values between 48 and 60 h after treatment. In marked contrast, none of the animals treated with LH-RH agonist showed this pattern of response. In the first test, five of the nine monkeys showed no rise in LH while in the remaining animals the response was diminished or delayed, and in the second test all none failed to show a significant rise in LH. In all agonist-treated monkeys oestrogen failed to cause an FSH rise in either test. Thus, chronic treatment with LH-RH agonist in the monkey either abolishes, diminishes or delays the oestrogen-induced LH surge. Since, in the primate, oestrogen appears to release LH by acting directly on the pituitary gland exposed to pulses of LH-RH from the hypothalamus it appears that the LH surge is inhibited primarily because the pituitary gland has been exposed to prolonged stimulation by the agonist.

Animals↗
PubMed1980

HCG stimulation of testicular LHRH-like activity.

It is well established that the administration of high doses of luteinizing hormone (LH) or human chorionic gonadotropin (HCG) to animals can impair gonadal function in both the male and female. These effects can be duplicated by the administration of LH releasing hormone (LHRH) or its agonists to intact animals, including man. Somewhat surprisingly, recent results have demonstrated that similar impairment of gonadal function by LHRH and its agonists can be achieved in the absence of the pituitary (for review see ref. 7), and the demonstration of specific, high-affinity binding sites for LHRH and its agonists on ovarian luteal cells and on testicular Leydig cells, could mean that LHRH-like factors are involved in the local regulation of the gonads. A further intriguing finding is the striking similarity between the direct, inhibitory effects of LHRH and LH/HCG on the gonads; for example, both treatments reduce LH receptor numbers and the steroidogenic responsiveness of rat Leydig cells. We now offer a possible explanation for this similarity by demonstrating that HCG treatment stimulates the testicular production of a biologically active LHRH-like factor, suggesting that the inhibitory actions of HCG on the Leydig cell may be mediated by the local production of this factor.

Animals↗
PubMed1980

Inhibition of maturational changes in Leydig cell function by treatment of rats with an agonist of LH-RH.

Daily treatment of immature (30-day-old) male rats for 40 days with 50 ng of an agonist of LH-RH impaired normal development of Leydig cell function. This treatment partly or completely inhibited maturational increases in (1) the serum levels of testosterone, (2) seminal vesicle weight, (3) the in-vitro steroidogenic responsiveness of the testis, and (4) the in-vitro testicular binding of 125I-labelled hCG. In contrast, twice-weekly treatment of immature or adult rats with 50 ng LH-RH agonist had only minor effects on Leydig cell function, although hCG-binding was always significantly reduced. Testicular growth in immature rats was unaffected by daily injection of LH-RH agonist whereas twice-weekly treatment caused a small reduction in weight. None of the treatments had any major consistent effect on the pituitary or serum levels of gonadotrophins and prolactin, although daily treatment with the LH-RH agonist clearly reduced the responsiveness of the pituitary to the agonist, in terms of the amounts of LH and FSH released.

Animals↗