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Biomedical subjects

D T Baird

Publications and source records attributed to D T Baird.

At least 271 records · Page 15Linked to original sources

Effect of enucleation of the corpus luteum at different stages of the luteal phase of the human menstrual cycle on subsequent follicular development.

To investigate the mechanism of suppression of follicular development during the luteal phase of the human menstrual cycle, the corpus luteum was enucleated surgically from 10 women at various times after ovulation. In the 24 h after CL enucleation there was an immediate and rapid fall in the concentration of oestradiol and progesterone and a temporary decline in the concentration of FSH and LH. Within 3 days, however, all 10 women showed evidence of renewed follicular activity as indicated by a progressive rise in the concentration of oestradiol. This rise was preceded by a rise in the concentration of FSH and LH, and ovulation, as indicated by a mid-cycle surge in LH and rise in the concentration of plasma progesterone, occurred 16-19 days after enucleation. There was no significant difference in the time to ovulation following enucleation at different times of the luteal phase. The post-operative follicular phase, measured from the time of enucleation, was 3 days longer than that observed pre-operatively from the first day of menstrual bleeding. In the follicular phase of post-operative cycles the concentration of FSH was higher and that of oestradiol lower than the corresponding values before surgery. These results indicate that the absence of healthy antral follicles in the luteal phase of the cycle is due to the inhibitory effects of the corpus luteum. The fact that, after CL enucleation, emergence of the dominant follicle was always preceded by a rise in the concentration of FSH and LH suggests that suppression of gonadotrophins by ovarian steroids secreted by the corpus luteum is responsible for the inhibition of follicular development during the luteal phase of the cycle.

Adult↗

Effect of immunoneutralization of LH releasing hormone on LH, FSH and ovarian steroid secretion in the preovulatory phase of the oestrous cycle in the ewe.

Immunoneutralization of LH releasing hormone (LHRH) by the i.v. administration of LHRH antiserum in the preovulatory period in the ewe resulted in a prompt abolition of the pulsatile secretion of LH without alteration of basal plasma levels of LH. This resulted in an immediate cessation of the pulsatile secretion of ovarian oestradiol, with no change in the secretion rate of androstenedione or plasma levels of FSH. The ovarian secretion rate of testosterone increased significantly. Twenty to 22h after the injection of LHRH antiserum, pulsatile secretion of LH and ovarian oestradiol and androgen secretion remained suppressed while plasma levels of FSH had increased significantly. The bolus injection of ovine LH (10 micrograms, i.v.) at this time caused a significant increase in oestradiol, androstenedione and testosterone, these responses being inversely related to the titre of LHRH antiserum in the plasma at this time. These results show that (1) the secretion of oestradiol from the preovulatory sheep follicle is entirely dependent on the pulsatile secretion of LH and (2) since the secretion of ovarian androgens was not inhibited, LH may exert a short-term control over the aromatase enzyme system controlling the conversion of androgen to oestrogen in the granulosa cell of the preovulatory sheep follicle.

Androstenedione↗

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↗

Is prostaglandin F2 alpha involved in the increased myometrial contractility of primary dysmenorrhoea?

The concentrations of prostaglandin F2 alpha (PGF2 alpha) and E2 (PGE2) in menstrual fluid collected daily from 13 women with primary dysmenorrhoea and 11 matched controls, were compared with the pattern of uterine contractility during the hour following the menstrual fluid collection. The intra-uterine pressure (IUP) was measured using a micro-transducer catheter and the tracings analysed. On Day 2 the concentration of PGF2 alpha correlated with the peak area, but not with amplitude, duration or rate of contraction. These findings add additional support to the hypothesis that increased production of PGF2 alpha could contribute to the increased uterine contractility in primary dysmenorrhoea.

Dinoprost↗

The effects of chronic treatment with LHRH on gonadotrophin secretion and pituitary responsiveness to LHRH in women with secondary hypogonadism.

Twenty women with secondary hypogonadism and four normal women in the early follicular phase of the cycle were treated for 7 days with 10, 50 or 100 micrograms synthetic LHRH administered intramuscularly at 4 h intervals. Concentrations of pituitary and ovarian hormones in plasma were measured at intervals during the treatment period. The episodic pattern of LH secretion and the gonadotrophin responses to acute stimulation with LHRH were evaluated before and after treatment. In normal women the concentrations of gonadotrophins and the LH response to LHRH remained unchanged, whilst the FSH response to LHRH was reduced after treatment. Concentrations of oestradiol rose progressively in response to treatment, indicating follicular development. In hypogonadal subjects with unimpaired pituitary function, treatment with LHRH induced a marked but transient increase in the concentrations of LH and FSH in plasma and a progressive rise in that of oestradiol. The concentration of progesterone was increased in four of the 11 subjects. However, the amplitude of LH pulses and the responses of FSH and LH to LHRH after treatment were suppressed below pretreatment values. Women with hypogonadotrophic hypogonadism and diminished pituitary responses to LHRH exhibited a sustained increase in the concentrations of LH, FSH and oestradiol in plasma to normal follicular phase levels. The amplitude of LH pulses and the LH response to LHRH were increased after treatment but did not reach normal values. The FSH response to LHRH was further reduced after treatment. Treatment of similar subjects with 10 micrograms LHRH induced a small increase in the concentration of gonadotrophins but not of ovarian steroids. These data demonstrate that the effect of chronic treatment with LHRH on women with secondary hypogonadism depends on the level of endogenous gonadotrophins. The dose of LHRH used in hypogonadal women receiving treatment by intermittent injection may require adjusting according to the level of gonadotrophin secretion if an optimal response is to be obtained.

Adult↗

Primary dysmenorrhoea: the importance of both prostaglandins E2 and F2 alpha.

Menstrual fluid was collected in a contraceptive diaphragm from 16 women with primary dysmenorrhoea and 12 matched control subjects without dysmenorrhoea. Prostaglandins F2 alpha (PGF2 alpha), E2 (PGE2) and 6-oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha) were extracted and measured using gas-chromatography: mass spectrometry (GC:MS). The concentrations of both PGF2 alpha and PGE2 were higher on days 1 and 2 in the dysmenorrhoea group than in the control group and the concentration of PGF2 alpha was higher on day 1 than on day 2 in the dysmenorrhoea group. The concentrations of 6-oxo-PGF1 alpha (the stable metabolite of PGI2) were low in both groups. These results confirm suggestions that PGF2 alpha is important in the aetiology of dysmenorrhoea and also indicate that PGE2 may be involved.

6-Ketoprostaglandin F1 alpha↗

Factors regulating the growth of the preovulatory follicle in the sheep and human.

Around the time of luteal regression in monovular species a single dominant follicle, which will eventually ovulate, is selected from the population of antral follicles. The dominant follicle is characterized by its progressive increase in diameter due to increase in antral fluid volume as well as an increased number of granulosa cells. The crucial factor in the continued development of the dominant follicle is its ability to synthesize oestradiol under the influence of LH and FSH. In the sheep FSH secretion continues throughout the luteal phase while LH is suppressed. Thus development of large antral follicles continues so that when luteal regression occurs and LH secretion increases the final stages of development of the pre-antral follicle occur within 3 days. In the human, however, both FSH and LH are suppressed during the luteal phase and only rise when the levels of progesterone and oestradiol fall a few days before menstruation. This rise in FSH and LH which occurs at this time stimulates the further development of a small antral follicle (1-2 mm diameter). Within 7 days the favoured follicle establishes dominance over the other asynchronously developing follicles probably by inhibiting the secretion of FSH. As in the sheep, once aromatase enzyme(s) has been fully activated the dominant follicle is able to utilize the increased androgen precursor produced by the theca under LH stimulation.

Animals↗

Direct effect of prolactin, induced by TRH injection, on ovarian oestradiol secretion in the ewe.

The effect of sustained high plasma levels of prolactin, induced by repeated 2-h i.v. injections of thyrotrophin-releasing hormone (TRH; 20 micrograms), on ovarian oestradiol secretion and plasma levels of LH and FSH was investigated during the preovulatory period in the ewe. Plasma levels of progesterone declined at the same rate after prostaglandin-induced luteal regression in control and TRH-treated ewes. However, TRH treatment resulted in a significant increase in plasma levels of LH and FSH compared to controls from 12 h after luteal regression until 5 to 6 h before the start of the preovulatory surge of LH. In spite of this, and a similar increase in pulse frequency of LH in control and TRH-treated ewes, ovarian oestradiol secretion was significantly suppressed in TRH-treated ewes compared to that in control ewes. The preovulatory surge of LH and FSH, the second FSH peak and subsequent luteal function in terms of plasma levels of progesterone were not significantly different between control and TRH-treated ewes. These results show that TRH treatment, presumably by maintaining elevated plasma levels of prolactin, results in suppression of oestradiol secretion by a direct effect on the ovary in the ewe.

Animals↗

Raised plasma oestrogens in infertile men with elevated levels of FSH.

In twenty oligospermic or azoospermic patients with elevated plasma FSH, the mean concentrations of plasma oestrone sulphate (843 +/- 233 pg/ml), oestrone (54 +/- 10.4 pg/ml) and oestradiol (46.6 +/- 12.6 pg/ml) were found to be significantly higher than in twenty-one normal fertile men of comparable age (593 +/- 220 pg/ml, 40.6 +/- 8.8 pg/ml and 33.1 +/- 10.9 pg/ml respectively). SHBG binding capacity was elevated in the infertile group (infertile 3.35 +/- 0.82 x 10(-8) M/l v. normal 2.76 +/- 0.89 x 10(-8) M/l) but the total plasma testosterone concentrations were comparable (infertile 5435 +/- 1578 pg/ml v. normal 5046 +/- 1102 pg/ml). Evidence was cited to support the view that Sertoli cells, in response to an unphysiological FSH stimulation, are a likely source of excessive oestrogen production. The possible significance of increased intra-testicular and circulating oestrogen in the altered state of testicular steroidogenic function in men with primary seminiferous tubular defects was discussed.

Adult↗

Assessment of pituitary secretory capacity in women with hypogonadotrophic hypogonadism by using a long-acting synthetic analogue of luteinizing hormone releasing factor.

The gonadotrophin responses to single and repeated injections of a long-acting synthetic analogue of luteinizing hormone releasing factor (LRF), d-Ser(TBU)6EA10LHRH, were investigated in 10 women with normoprolactinaemic hypogonadotrophic hypogonadism. Abnormal luteinizing hormone (LH) responses were observed in two of the five patients treated with 5 micrograms of the analogue and in all five patients treated with three injections of 10, 20 and 10 micrograms administered at intervals of 10-14 h. However, the LH response to repeated injections of the analogue was of similar magnitude and duration to that observed in normal women in response to an oestrogen provocation test in the early-to-mid follicular phase of the cycle. Thus failure of the LH response to oestrogen provocation in women with hypogonadotrophism results from hypothalamic rather than primary pituitary dysfunction. This study confirms the usefulness of this analogue of LRF in the assessment of pituitary secretory function in women with abnormal responses to oestrogen positive feed-back.

Buserelin↗

The synthesis of prostaglandins from persistent proliferative endometrium.

The pattern of prostaglandins (PGs) synthesized by persistent proliferative endometrium of women with excessive menstrual bleeding (greater than 50 ml) associated with anovulatory cycles was compared to endometrium collected from women with normal menstrual blood loss (less than 50 ml). Levels of PGF2 alpha in normal and persistent proliferative endometrium were lower than the levels of PGF2 alpha found in normal secretory endometrium (P less than 0.005 for both normal and persistent proliferative endometria). When incubated with exogenous [1-14C]arachidonic acid (9.1 nmol), normal secretory endometrium synthesized more PGF2 alpha and PGE2 than did normal proliferative endometrium, but the amounts of PGF2 alpha and PGE2 released by persistent proliferative endometrium were similar to those obtained by normal secretory endometrium. These findings suggest that persistent proliferative and normal secretory endometria have the same PG synthetase activity, and that the low endogenous concentrations of PGF2 alpha in the former arise from a lack of endogenous precursor. PGF2 alpha has predominantly vasoconstricting properties, and a reduced capacity to synthesize this PG by persistent proliferative endometrium may result in excessive menstrual bleeding, as was suggested by the inverse correlation between the ratio of the endogenous concentrations of PGF2 alpha and PGE and the menstrual blood loss (r = -0.7; P less than 0.005; n = 26).

Adult↗

Human testis does not secrete oestrone sulphate.

The concentrations of five steroids in samples of spermatic venous blood collected from 17 men undergoing ligation of varicocoeles were compared with those in samples from the antecubital vein. There was evidence of testicular secretion of testosterone, androstenedione, oestradiol-17 beta and oestrone, since the ratios of the mean concentrations in spermatic venous plasma to those in peripheral venous plasma were 77.2, 9.1, 28.7 and 1.6 respectively. The testicular secretion of oestrone sulphate was minimal; the ratio of the mean concentrations in spermatic and peripheral plasma was 1.07. These results support the view derived from isotope dilution studies that almost all oestrone and oestrone sulphate in the circulation is derived from peripheral conversion of other precursor steroids.

Adolescent↗

A role for prostacyclin (PGi2) in excessive menstrual bleeding.

The synthesis of prostanoids from arachidonic acid incubated with endometrium alone or together with myometrium was studied in women with excessive menstrual blood-loss (range 57--186 ml, median 86 ml). Production of prostaglandins F2 alpha, E2, and D2 was similar to that observed for the endometrium of women with normal periods (range 5--50 ml; median 11 ml). However, the endometrium from women with excessive menstrual blood-loss was more effective than endometrium from women with normal menstrual blood-loss at enhancing the production by a control preparation of myometrium of 6-oxo-prostaglandin F1 alpha, the stable metabolite of prostacyclin. The ability of the uterus to generate prostacyclin, a prostaglandin known to inhibit platelet aggregation and stimulate vasodilatation, may influence the degree and duration of menstrual bleeding.

6-Ketoprostaglandin F1 alpha↗

Morphological and functional relations of Graafian follicle growth to ovulation in women using ultrasonic, laparoscopic and biochemical measurements.

The daily growth rates of ovarian follicles were recorded ultrasonically for five days until ovulation in 56 spontaneously ovulating women and related to endocrine and clinical parameters. Over the 5-day period, the average diameter of the follicle destined to ovulate increased from 12 to 23 mm, the second largest follicle from 6 to 12 mm, the third largest follicle from 5 to 9 mm and the fourth largest follicle from 4 to 8 mm. Similar but lesser growth rates occurred in the follicles in the contralateral ovary. Ovulation occurred within 24 hours of the luteinizing hormone (LH) peak, and the mean peak diameter of the ovulating follicle was 23.2 +/- 0.3 (SEM) mm, (range 18-29 mm) before ovulation, and subsequent luteal function was judged to be normal. Follicular growth was most closely correlated with increasing peripheral blood oestrogen levels. In 16 women who had a laparoscopy within 12 hours of the last ultrasound and following the LH peak, the mean diameter of the largest follicle as measured by ultrasound (23.6 +/- 0.4 mm) was similar to that measured at laparoscopy (22.8 +/- 0.04 mm) and estimated from the volume of follicular fluid aspirated (average 5.8 +/- 0.2 ml), 22.5 mm. The follicular fluid levels of progesterone were high on the day of the LH peak and blood progesterone levels had risen significantly indicating that luteinization of the dominant Graafian follicles had already occurred prior to ovulation. This study confirms that ultrasonic monitoring provides a reliable measure of follicular growth and allows studies correlating morphological changes with both normal and abnormal endocrine function of the human ovary.

Adult↗