Biomedical subjects

H M Fraser

Publications and source records attributed to H M Fraser.

At least 73 records · Page 4Linked to original sources

PubMed1996

Luteinizing hormone receptor in the human corpus luteum: lack of down-regulation during maternal recognition of pregnancy.

Luteal progesterone production is dependent on luteinizing hormone (LH) from the pituitary gland. Despite continuing LH secretion, the human corpus luteum undergoes functional luteolysis unless it is 'rescued' by human chorionic gonadotrophin (HCG), produced by the implanting blastocyst. As LH and HCG act through a common receptor, this study sought to determine the expression of the LH/ HCG receptor in the corpus luteum during maternal recognition of pregnancy. Corpora lutea were collected at hysterectomy from women in the normal luteal phase and after luteal 'rescue' with exogenous HCG. In each case the corpus luteum was classified according to the date of the LH surge measured in daily urine samples. The expression of the LH receptor was investigated by Northern blotting, in-situ hybridization and in-situ ligand binding. LH receptor mRNA and ligand binding activity were detected in corpora lutea from all stages of the luteal phase. LH receptor expression and binding were maintained during maternal recognition of pregnancy in the presence of exponentially increasing HCG concentrations. These data show that the LH receptor is maintained throughout the functional life-span of the human corpus luteum and is not down-regulated during maternal recognition of pregnancy.

Adult↗

PubMed1996

The neonatal period: a critical interval in male primate development.

It appears from the evidence documented in this Commentary that the neonatal period is another critical stage in the process of sexual, behavioural and immune system development and maturation in primates. Interference with normal brain-pituitary-gonadal function during this period (e.g. with a GnRH analogue in monkeys) appears to impact adversely on subsequent reproductive, immunological and behavioural function. These data further emphasize the importance of fully understanding the regulatory mechanisms that govern neonatal gonadal function in the primate, if we are to eliminate, control or minimize the potential risk resulting from its disruption in humans. Given the recent evidence that the reproductive potential of the human male has declined rather dramatically over the last 50 years, and that clinical conditions associated with abnormal testicular function are on the rise, continued investigation in this area would appear to be imperative.

Animals↗

PubMed1996

Expression of tissue inhibitor of metalloproteinases-1 in the primate ovary during induced luteal regression.

Although tissue inhibitor of metalloproteinases-1 (TIMP-1) is one of the major secretory products of the corpus luteum, the functional significance of this is not clear. In addition to its role as a specific inhibitor of the matrix metalloproteinase enzymes involved in tissue remodelling, it has recently been suggested that TIMP-1 is also a potent stimulator of steroidogenesis in vitro. However, in the ruminant, TIMP-1 expression increases during luteal regression. This study sought to determine (i) the effect of induced luteal regression on ovarian TIMP-1 expression in the primate and (ii) the expression of TIMP-1 in other steroidogenic and non-steroidogenic tissues. Marmoset ovaries were studied on day 10 of the normal luteal phase and 12 and 24 h after induced luteolysis, with either gonadotrophin-releasing hormone (GnRH) antagonist or prostaglandin F2 alpha analogue. Ovaries from different stages of the normal ovarian cycle were also studied. Expression of TIMP-1 was investigated by isotopic in situ hybridisation. TIMP-1 expression was also examined in a wide range of other marmoset tissues by Northern blotting and in situ hybridisation. TIMP-1 was found to be highly expressed in the marmoset corpus luteum. Luteolysis induced with either prostaglandin F2 alpha or GnRH antagonist was associated with a significant fall in TIMP-1 expression in luteal tissue. TIMP-1 mRNA was also localised to ovarian follicles throughout the ovarian cycle. Expression occurred in the thecal layer of smaller follicles (< 1.5 mm) and the granulosal layer of larger pre-ovulatory follicles. In atretic follicles, TIMP-1 was highly expressed at the interface between the thecal and granulosal cells. TIMP-1 was found to be predominantly expressed in steroidogenic tissues, particularly the ovary, adrenal and placenta. These data support a role for changes in TIMP-1 expression in tissue remodelling in the ovary and are consistent with an additional function of TIMP-1 as a facilitator of steroidogenesis.

Animals↗

PubMed1995

Immunolocalization of bcl-2 in the human corpus luteum.

The mechanisms of luteal regression and rescue in women are unknown but forms of programmed cell death may be involved. The proto-oncogene bcl-2 is an important inhibitor of apoptosis but has not previously been described in the human corpus luteum. Immunohistochemical localization of bcl-2 protein was investigated in human corpora lutea obtained from women undergoing surgery during endocrine monitored menstrual cycles as well as from women who had been treated with human chorionic gonadotrophin (HCG) to prolong the luteal phase. Bcl-2 was found to be localized in granulosa-lutein, theca-lutein (as identified by co-localization of P450(17)alpha-hydroxylase) and the endothelial cells around some blood vessels. Immunoblotting demonstrated the presence of a single band of approximately MW 26 kDa. There was no apparent change in either the intensity of immunostaining or the histological localization during the normal luteal phase or following treatment with human chorionic gonadotrophin. The product of the proto-oncogene bcl-2 is present in the human corpus luteum. It is unlikely that bcl-2 expression alone is responsible for prolongation of the lifespan of the corpus luteum in early pregnancy although it is possible that the action of the bcl-2 gene present is modified by changes in other members of the bcl-2 family.

Adult↗

PubMed1995

Induced luteal regression: differential effects on follicular and luteal inhibin/activin subunit mRNAs in the marmoset monkey.

During the luteal phase of the primate ovulatory cycle the predominant inhibin/activin subunit mRNAs produced by the corpus luteum and antral follicles are those for the alpha- and beta B-subunits respectively. The control of expression of these mRNAs and the resultant nature of the endocrine and paracrine signals which they may potentially generate has yet to be elucidated. Inhibin/activin subunit mRNAs may have a role in both the paracrine regulation of follicular and luteal function and modulation of FSH secretion. The aim of this study was to investigate the expression of inhibin/activin subunit mRNAs following luteal regression induced by either withdrawal of LH support (GnRH antagonist treatment), or by a direct inhibitory action (prostaglandin administration). Marmoset monkeys with regular ovulatory cycles were treated on day 8 and 9 of the luteal phase with either GnRH antagonist, prostaglandin or vehicle (n = 3 per group). Ovaries were studied 48 h after onset of treatment (on day 10 of the luteal phase) by hybridizing frozen tissue sections with radiolabelled riboprobes specific to the inhibin/activin alpha-, beta A- and beta B-subunit mRNAs. After autoradiographic exposure, grain concentrations were quantified by image analysis. In corpora lutea from control marmosets there was high expression of alpha-mRNA with only marginal expression of beta B-mRNA. Corpora lutea in animals treated with GnRH antagonist or prostaglandin had markedly reduced expression of alpha-mRNA while beta B-mRNA was unchanged. In controls, all healthy antral follicles exhibited a high level of expression of beta B-mRNA in the granulosa cells and low expression of alpha-mRNA in theca cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Activins↗

PubMed1995

Induced luteal regression in the primate: evidence for apoptosis and changes in c-myc protein.

There is increasing molecular evidence that apoptosis is involved in the process of structural luteal regression in non-primate species. Apoptosis is dependent upon the activation of certain proto-oncogenes and c-myc protein has an important regulatory role in this process in some cell types. The aim of the present study was to determine the occurrence and localisation of c-myc protein within the primate corpus luteum, determine changes during induction of luteal regression and examine the corpora lutea for morphological evidence of apoptosis. Ovaries were studied from marmoset monkeys in the late follicular, and in the early, mid and late luteal phases. Luteal regression was induced either by treatment with prostaglandin F2 alpha analogue or GnRH antagonist administered during the mid luteal phase and ovaries obtained 24 and 48 h later. Immunocytochemistry was performed using a monoclonal antibody to the c-myc protein. In pre-ovulatory follicles positive staining was found in the nucleus of a few granulosal cells and in the cytoplasm of thecal cells. c-myc was present in all corpora lutea where it was localised predominantly in the cytoplasm. In early corpora lutea, scattered cells with intense staining were observed in the presence of a majority of moderately or weakly stained cells. In the mid and late luteal phases, corpora lutea were uniformly moderately stained for c-myc. Following induction of luteal regression, regression, nuclear degeneration with condensation and fragmentation indicative of apoptosis was observed. In other luteal cells, increased membranes suggested necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Gonadotropin-releasing hormone antagonist for postpartum contraception: outcome for the mother and male offspring in the marmoset.

GnRH antagonists have potential for use in postpartum contraception, as it is likely that they would be effective in maintaining the inhibition of ovulation associated with lactation, but possible effects on the infant by transfer of antagonist via breast milk are unknown. The aim of this study was to establish whether chronic treatment with a GnRH antagonist would prevent ovulation throughout the period of lactation using the marmoset monkey as a model and to evaluate the effects of the presence of GnRH antagonist in breast milk on the postnatal rise in plasma testosterone concentrations in male infants. Mothers who had delivered male twins were selected. Starting within 3 days postpartum, mothers (n = 5/group) were treated with either 6.0 or 0.6 mg/kg of the GnRH antagonist antide, sc, once per week for 11 weeks. Ten postpartum lactating females acted as controls. All animals were housed in family groups with fertile males. To determine possible effects on the postnatal rise in testosterone, plasma samples were collected from the male infants of the high dose antide-treated mothers at weekly intervals for 12 weeks. Plasma progesterone concentrations were monitored in lactating mothers until establishment of pregnancy in both treated and control groups. Concentrations of antide were determined by RIA in plasma from mothers in the high dose group, in their milk, and in pooled plasma samples from their infants. Ovulation followed by pregnancy occurred in all of the control animals. No ovulations occurred during treatment with antide. Antide was present throughout treatment in plasma and breast milk in the mother. In male infants feeding from mothers receiving high dose treatment, antide was not detectable in infant plasma, and plasma testosterone concentrations were within the normal range for male neonates in our colony. These results indicate that the GnRH antagonist has potential as a method of contraception postpartum without affecting the postnatal rise in testosterone in male infants.

Animals↗

PubMed1994

Blockade of the neonatal rise in testosterone by a gonadotrophin-releasing hormone antagonist: effects on timing of puberty and sexual behaviour in the male marmoset monkey.

In primates, plasma testosterone concentrations are elevated for some 3 months from birth. The function of this rise is uncertain, but studies in rats suggest that its prevention by castration or administration of gonadotrophin hormone-releasing hormone (GnRH) analogues has effects on development and expression of social and sexual behaviours, and adverse long-term effects on fertility. The consequences of suppression of this rise in testosterone by treatment with the GnRH antagonist antide have been investigated in the marmoset monkey. Eight sets of male:male twins were used, one of each set receiving s.c. injections of antide (10 mg/kg), on days 0, 3 and 7, then weekly from birth to 98 days of age, with the twin receiving vehicle only. Plasma samples were taken at weekly intervals for the determination of testosterone concentrations from birth until 2 years of age. Treatment with antide completely abolished the neonatal rise in testosterone seen in control animals. The timing of the onset of the pubertal testosterone rise was not significantly affected by treatment; however, the subsequent pattern of circulating testosterone showed a tendency to decreased plasma concentrations in the neonatally treated group from weeks 25 to 42, relative to controls, and this difference was significant between 43 and 70 weeks. This was associated with a similar depression in bioactive LH concentrations around this time. Thereafter, the testosterone concentrations were similar between treated and control groups. There was no effect of treatment on growth, based on sequential body weight data. At 20 months the animals underwent behaviour tests with ovariectomized females.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Manipulation of inhibin during the luteal-follicular phase transition of the primate menstrual cycle fails to affect FSH secretion.

The pattern of inhibin concentrations in blood during the menstrual cycle in primates has suggested an endocrine role of inhibin in the negative feedback control of FSH secretion during the luteal phase. Conversely, the fall in inhibin during the late luteal phase may play a role in the rise in serum FSH during the luteal-follicular phase transition. This hypothesis was examined by determining the effects of manipulation of inhibin on FSH secretion in stumptailed macaques. During the mid-luteal phase the putative inhibin feedback was inhibited by i.v. administration of 20 ml of ovine antiserum to human recombinant inhibin in 4 macaques. FSH secretion was unaffected during the initial 24 h period post-treatment and the timing of the rise in FSH which occurred during the subsequent luteal-follicular phase transition was normal. To determine whether the elevated serum concentrations of FSH observed during the early follicular phase could be reduced by administration of inhibin, 5 cyclic macaques were treated with 200 micrograms of recombinant human inhibin i.v. Serum FSH concentrations were unaltered. These results suggest that inhibin does not play a major role in modulating FSH secretion during the luteal-follicular phase transition.

Animals↗

PubMed1993

GnRH analogues for contraception.

The production of chemical analogues of GnRH permits direct suppression of the pituitary-gonadal axis at the level of the gonadotroph. Continuous administration of GnRH agonists desensitizes the gonadotroph and ovulation is uniformly prevented, forming the practical basis for use in contraception. However, long-term treatment is constrained by variable effects on oestrogen secretion, which cause irregular bleeding patterns on the one hand and risks of hypo-oestrogenism on the other. Their use as a post-partum contraceptive has attractions because any analogue in milk should be without biological activity in the infant. GnRH antagonists have the advantage of immediate inhibitory action. They have potential application in circumstances in which agonists have been employed and, in addition, can interrupt any stage of the menstrual cycle. Clinical trials to utilise their potential antifertility action have not been performed. Use of GnRH analogues for contraception in women may require combination with low dose oestrogen and progestin and it has been proposed that such development may yield important benefits in health. When combined with testosterone, GnRH antagonists may form the basis for a male contraceptive.

Contraceptives, Oral, Hormonal↗

PubMed1993

Puberty in the male chimpanzee: time-related variations in circulating inhibin.

Circulating immunoreactive inhibin concentrations were determined in male chimpanzees (n = 12) during a 36-mo period starting 18 mo before the onset of pubertal testicular growth (Po). Serum levels of inhibin started to increase, together with LH and testosterone, 6 mo before a rise in FSH and Po. Before Po, inhibin was not related to gonadotropins but was related to testosterone levels (r = 0.263; p < 0.005; R2 = 7%). After Po, inhibin remained related to testosterone (r = 0.289, p < 0.01) but became inversely related to gonadotropins; FSH was the best predictor (r = -0.382, p < 0.0005; R2 = 30%) of this relationship. During the progressive rise in circulating inhibin, FSH increased and plateaued during 9 mo, then dropped to prepubertal levels. These findings suggest that a specific closed-loop negative feedback system for the secretion of FSH by inhibin is not functional before the onset of puberty in the chimpanzee. This feedback system seems to fully operate several months after the LH rise and may be related to the complete maturation of both Sertoli cells and spermatogenesis.

Animals↗

PubMed1993

Intratesticular hormone levels and the route of secretion of hormones from the testis of the rat, guinea pig, monkey and human.

Blood samples were obtained from the testes of rats, guinea pigs and Macaque monkeys and from normal men undergoing vasectomy reversal, in order to assess the comparative dynamics of hormone secretion. In each species, blood was sampled from a vein on the surface of the testis (testicular venous blood, TV), from a vein in the spermatic cord above the pampiniform plexus (spermatic venous blood, SV) and from a vein elsewhere in the body (peripheral venous blood, PV). Plasma concentrations of testosterone and inhibin were then determined by radioimmunoassay. In all species, testosterone secretion profiles were comparable, with concentrations being greatest in TV blood. SV concentrations were reduced by 40-60% compared with TV levels, with a significantly greater reduction in PV levels. Inhibin secretion varied significantly between species, with the rat being the only animal to show significant increases in inhibin concentrations from TV to SV blood. Inhibin secretion in the guinea pig was most comparable with that of the rat, although the increased SV levels fell short of being significant. Macaque and human profiles contrasted with those of the rat and guinea pig, with the greatest inhibin concentrations being found in TV blood. Levels in SV blood were reduced by some 40%, and PV levels were reduced significantly further. These differences may be due to the different position of the rete testis, and its relationship to the testicular vasculature, in these species. The sampling procedure described provides a defined set of testicular blood samples that could contribute important information of relevance to physiological and clinical studies of testicular function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Localization of inhibin/activin subunit mRNAs during the luteal phase in the primate ovary.

Localization of inhibin/activin subunit mRNAs within the macaque ovary from the immediate pre-ovulatory period of the menstrual cycle, when serum immunoreactive inhibin begins to rise, to day 9 of the luteal phase, when serum inhibin concentrations are maximal, was investigated using in-situ hybridization. Ovaries were studied on the day of the LH surge (day 0) and on days 2, 5, and 9 of the luteal phase by hybridizing frozen tissue sections with radiolabelled riboprobes specific to the inhibin/activin alpha-, beta A- and beta B-subunits. After autoradiographic exposure for 10 and 21 days, grain concentrations were quantified by image analysis. Moderate expression of alpha-, beta A- and beta B-subunit mRNA was present within the granulosa cells of the pre-ovulatory follicle (day 0). The granulosa-lutein cells of the corpora lutea expressed high levels of alpha-subunit at days 2, 5 and 9. mRNAs for beta A and beta B were detected at low but significant levels in all of the corpora lutea. All healthy antral follicles exhibited a high level of expression of beta B-subunit mRNA in the granulosa cells. On day 2 after ovulation these follicles also expressed high alpha- and moderate beta A-subunit mRNA. On day 9 the beta B-inhibin mRNA in antral follicles was found in association with low expression of the other subunits. Small follicles in ovaries on day 2 expressed moderate alpha- and low levels of beta B-subunit mRNA, while mRNA for beta A was absent. alpha-subunit mRNA expression was present on day 5 while neither beta A- nor beta B-subunit mRNA was detected. On day 9 a proportion of small follicles expressed alpha- and beta A-subunit mRNA. These results demonstrate that marked differences are present in the levels of expression of the three inhibin/activin subunit genes between follicles and the corpus luteum. The predominance of the beta B-subunit mRNA within antral follicles would be consistent with the synthesis of activin. The predominance of the alpha-subunit combined with the low expression of the beta-subunits in the corpus luteum suggests that both biologically active inhibin and free alpha-subunit are produced by the primate corpus luteum.

Activins↗

PubMed1992

Long-acting gonadotrophin releasing hormone agonist implant causes variable duration of suppression of ovarian steroid and inhibin secretion.

OBJECTIVE: The duration of action of a gonadotrophin releasing hormone (GnRH) agonist implant designed to be effective for 3 months was investigated in women by monitoring drug release and ovarian hormone secretion. Serum inhibin secretion was measured to determine whether the secondary rise in serum FSH concentrations observed during long-term GnRH agonist treatment was attributable to changes in inhibin secretion. DESIGN AND PATIENTS: The implants of slowly biodegradable polylactide/glycolide (molar ratio 75:25) containing 3.3 mg buserelin, D-Ser (But)6-GnRH (1-9)-nonapeptide-ethylamide, in a rod 1 cm long and 0.13 cm diameter were injected s.c. in patients with endometriosis (3.3 mg buserelin in four patients, 6.6 mg buserelin in six patients). MEASUREMENTS: Urinary secretion of oestrone, pregnanediol, LH and buserelin were determined in daily samples collected for 2 cycles before treatment, during treatment, and for 2 recovery cycles. Oestradiol, progesterone, inhibin, LH and FSH were measured in serum collected once per week. RESULTS: In all patients ovarian hormone secretion was suppressed successfully but considerable variability occurred in the length of time taken for ovarian function to recommence, time to return to ovulation being 100-194 days (median 118 days) (3.3 mg group) and 79-290 (median 178 days) (6.6 mg group). After implant injection, there was a rapid rise in the urinary buserelin excretion followed by an early fast phase of buserelin release, half life (t1/2) = 9 days for 3.3 mg implant and 11 days for 6.6 mg implant. This was followed by a second phase representing a plateau of release, t1/2 = 50 days (3.3 mg implant) and 90 days (6.6 mg implant). During this second phase, an excretion rate of greater than 0.2 nmol buserelin/mol Cr was associated with oestrone excretion at or below early follicular phase values. Once buserelin excretion fell below 0.1 nmol/mol Cr, ovarian function returned in all patients. The period for which buserelin secretion was maintained between 0.1 and 0.2 nmol/mol Cr corresponded to the time taken to recovery of ovulatory cycles in 8/10 of the women. In 9/10 patients serum immunoreactive inhibin concentrations declined at 2 weeks, along with the suppression of oestradiol, and remained suppressed throughout the period of anovulation. Recovery of FSH secretion began after 4-5 weeks. CONCLUSIONS: While this implant should have important clinical application where chronic treatment is indicated, further work is needed on design of long-term implants so that such preparations can be used when precise return to ovarian activity is required. A fall in inhibin secretion may contribute to the secondary rise in FSH by withdrawal of negative feedback but these events are not closely correlated.

Adult↗

PubMed1992

Suppression of pulsatile luteinizing hormone secretion by gonadotrophin-releasing hormone antagonist does not affect episodic progesterone secretion or corpus luteum function in ewes.

Progesterone secretion has been observed to be episodic in the late luteal phase of the oestrous cycle of ewes and is apparently independent of luteinizing hormone (LH). This study investigated the effects of suppressing the pulsatile release of LH in the early or late luteal phase on the episodic secretion of progesterone. Six Scottish Blackface ewes were treated i.m. with 1 mg kg-1 body weight of a potent gonadotrophin-releasing hormone (GnRH) antagonist on either day 4 or day 11 of the luteal phase. Six ewes received saline at each time and acted as controls. Serial blood samples were collected at 10 or 15 min intervals between 0 and 8 h, 24 and 32 h, and 48 and 56 h after GnRH antagonist treatment and daily from oestrus (day 0) of the treatment cycle for 22 days. Oestrous behaviour was determined using a vasectomized ram present throughout the experiment. Progesterone secretion was episodic in both the early and late luteal phase with a frequency of between 1.6 and 3.2 pulses in 8 h. The GnRH antagonist abolished the pulsatile secretion and suppressed the basal concentrations of LH for at least 3 days after treatment. This suppression of LH, in either the early or late luteal phase, did not affect the episodic release of progesterone. Daily concentrations of progesterone in plasma showed a minimal reduction on days 11 to 14 after GnRH antagonist treatment on day 4, although this was significant (P < 0.05) only on days 11 and 13. There was no effect of treatment on day 11 on daily progesterone concentration, and the timing of luteolysis and the duration of corpus luteum function was unaffected by GnRH antagonist treatment on either day 4 or day 11. These results indicate that the episodic secretion of progesterone during the luteal phase of the oestrous cycle in ewes is independent of LH pulses and normal progesterone secretion by the corpus luteum can be maintained with minimal basal concentrations of LH.

Analysis of Variance↗

PubMed1992

Influence of the gonad on the degree of suppression induced by an LHRH agonist implant in the marmoset monkey.

In a previous study pituitary-testicular function was shown to be maintained in a New World primate after the administration of an LHRH agonist implant. In the present study the mechanism of action of the same LHRH agonist (buserelin) on pituitary-gonadal function in the marmoset was investigated and a comparison made between the effects of treatment in three intact males, six adult cyclic females with regular ovulatory cycles, and six long-term ovariectomized animals. These were injected s.c. with an LHRH agonist implant (1.5 mg buserelin in a rod 0.5 cm long). In both the males and intact females, basal plasma LH concentrations were maintained within the normal range throughout the expected duration of agonist action (at least 3 months). Despite this, an absence of response to an LHRH challenge indicated that pituitary desensitization had occurred. In the intact females, ovulation was inhibited in five of six animals, plasma progesterone concentrations initially being maintained but subsequently remaining suppressed until 136 +/- 18 (S.E.M.) days after treatment. Responsiveness to administered LHRH returned prior to onset of return to ovarian cycles. In contrast, in ovariectomized marmosets, plasma LH was markedly suppressed to concentrations which were at or below the limit of detection of the assay and were therefore less than those observed in the buserelin-implanted intact animals. These results show that apparently normal pituitary-gonadal function in this species disguises an underlying pituitary desensitization to LHRH. This allows continuation of testosterone secretion in the male, but in the female ovulation is prevented, presumably as a result of failure of the desensitized pituitary to produce an LH surge.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Immunoneutralization and immunocytochemical localization of inhibin alpha subunit during the mid-luteal phase in the stump-tailed macaque.

The putative endocrine role of inhibin in the control of FSH secretion during the luteal phase in the primate was investigated by immunoneutralization. Antisera against the 1-23 amino acid sequence of the N-terminus of the human inhibin alpha subunit were raised in a ewe and three macaques. Antisera (10-20 ml) were administered to macaques on day 8/9 of the luteal phase and serum samples collected during the treatment cycle and post-treatment cycle for determination of FSH, oestradiol and progesterone. In addition, localization of inhibin within the macaque ovary at this stage of the luteal phase was investigated using the ovine antiserum. Intense immunostaining was localized within the granulosa-lutein cells of the corpus luteum with absence of staining in the theca-lutein cells or other ovarian compartments. Administration of antisera was without significant effect on serum concentrations of FSH when compared with control animals, either during the first 24 h of detailed observation or for the following 10-day period of the late luteal phase and subsequent early follicular phase. These results provide further evidence that the corpus luteum is the major source of inhibin immunoreactivity during the primate menstrual cycle, but fail to support an endocrine role for inhibin in the suppression of FSH secretion.

Animals↗

PubMed1991

Effect of late follicular phase administration of antide on ovulation and inhibin secretion in macaques.

In previous studies, the LHRH antagonist detirelix, administered to stumptailed macaques during the menstrual cycle, was only partially effective in blocking pituitary-ovarian function when given during the late follicular phase. Since the antagonist was suppressive when administered during the early luteal phase, we investigated the ability of antide, a putative long-acting LHRH antagonist, to cause inhibition of the LH surge or luteal function when administered during the late follicular phase. Six animals with regular ovulatory cycles were treated on day 10 of the follicular phase with 1mg/kg antide s.c. All animals demonstrated a continued rise in serum concentrations of estradiol which were followed by an LH surge beginning 2-5 days after antide injection and serum progesterone and inhibin secretion which indicated normal luteal function. In a second experiment, six animals were treated on day 10 of the follicular phase with 3mg/kg antide s.c. In three animals, this caused a fall in serum concentrations of estradiol and the expected LH surge and rises in progesterone and inhibin secretion indicating ovulation failed to occur. In 2 animals, the LH surge was not prevented but the consequential rise in progesterone and inhibin was attenuated. In the remaining animal the cycle appeared unaffected. Pharmacokinetics of antide revealed an initial high release rate during the first 4 days (1mg/kg) or 6 days (3mg/kg) followed by a period of sustained release at a relatively low level. These results show that antide is partially effective in blocking ovulation at a high dose in the macaque and may result in an inadequate luteal phase, presumably as a result of its extended action.

Animals↗