Ovine follicular fluid suppresses the ovarian secretion of androgens, oestradiol and inhibin

1990 ◽  
Vol 127 (1) ◽  
pp. 23-32 ◽  
Author(s):  
D. T. Baird ◽  
B. K. Campbell ◽  
A. S. McNeilly

ABSTRACT An experiment was conducted to examine the effect of steroid-free ovine follicular fluid (oFF) on ovarian hormone secretion. Eight Merino × Finnish Landrace ewes in which the left ovary and vascular pedicle had been autotransplanted to a site in the neck were studied during the breeding season. Luteal regression was induced in all animals by injection of cloprostenol (100 μg, i.m.) on day 10 of the luteal phase. Four of the eight animals were treated with steroid-free oFF (3 ml, s.c.) in the early follicular phase, 24 and 36 h after injection of cloprostenol. Samples of both ovarian and jugular venous blood were collected at 4-h intervals from 20 h before until 96 h after injection of cloprostenol. Ovarian and jugular venous blood samples were also collected at 10-min intervals from 48 to 52 h after injection of cloprostenol to investigate the pattern of pulsatile secretion of ovarian hormones. Samples were assayed for oestradiol, androstenedione, testosterone and inhibin and the ovarian secretion rates calculated. Both injections of oFF resulted in a fourfold increase in the concentration of inhibin in jugular venous plasma within 4–8 h of administration (P < 0·01) with concentrations remaining increased (P < 0·05) until 56 h after cloprostenol (32 h after the first oFF injection). Following oFF injection there was a profound (100%; P < 0·001) and prolonged decrease in the peripheral concentration of FSH until 60 h after cloprostenol at which time the concentration of FSH increased five- to sixfold (P < 0·001) to a peak lasting 24 h. In contrast to FSH, the concentration of LH in jugular venous plasma rose immediately following oFF treatment and continued to increase, exhibiting a profile similar to that described for FSH. No preovulatory LH surge was detected in any of the oFF-treated ewes while untreated ewes had an LH surge within 58·0±1·2 (s.e.m.) h. Within 8 h of the first injection of oFF the ovarian secretion rate of oestradiol, androstenedione and inhibin began to decline to reach a nadir of less than 1 ng/min within 32–36 h (56–60 h after cloprostenol; P < 0·01). Testosterone secretion, already barely detectable, did not change significantly following injection of oFF but remained low for 36 h following oFF and did not exhibit the increase observed over this period in controls. After injection of oFF the episodic secretion of oestradiol, androstenedione, testosterone and inhibin was markedly suppressed in spite of numerous pulses of LH. Re-establishment of inhibin, androstenedione and testosterone secretion began from around 36 h after injection of oFF and continued to increase for the remainder of the experimental period (P < 0·001). The re-establishment of oestradiol secretion, however, took until 60 h after oFF treatment (84 h after cloprostenol). This increase in ovarian hormone secretion was temporally related to the decrease in the concentration of FSH and LH in jugular venous plasma that was observed at the end of the experimental period. We conclude that treatment of ewes with steroid-free oFF during the follicular phase of the oestrous cycle results in the immediate inhibition of the ovarian secretion of oestradiol, inhibin, androstenedione and testosterone. This effect can most probably be attributed to the depression in FSH that occurs following oFF injection, although the possibility exists that other factors present in oFF are acting directly on the ovary to inhibit follicular growth. Journal of Endocrinology (1990) 127, 23–32

1996 ◽  
Vol 149 (3) ◽  
pp. 531-540 ◽  
Author(s):  
B K Campbell ◽  
R J Scaramuzzi

Abstract Recombinant human inhibin A (rhInh) or steroid-free bovine follicular fluid (bFF) were infused into the ovarian artery of anoestrous ewes with ovarian autotransplants induced to ovulate with a pulsatile regimen of GnRH applied after a 10-day pretreatment with progestagen sponges. In the period 12–24 h after sponge withdrawal ewes received ovarian arterial infusions of saline (n=6), 0·3 μg rhInh/h (n=5), 1·6 μg rhInh/h (n=5) or 25 μl bFF/h (n=4). Controls had a normal follicular phase with an LH surge 43 ± 3 h after sponge withdrawal which resulted in ovulation (six out of six). Both doses of rhlnh increased ovarian venous inhibin concentrations in a dose-related fashion (P<0·05) but resulted in depressions (P<0·05) in FSH concentrations of similar magnitude. Both doses of rhInh acutely inhibited ovarian oestradiol and androstenedione secretion (P<0·01) but at the end of rhInh infusion oestradiol secretion was quickly re-established without a corresponding increase in FSH. LH surges were detected in five out of five and three out of five ewes infused with low and high doses of rhInh respectively, and progesterone concentrations during the subsequent luteal phase were depressed (P<0·05). Infusion of bFF had no effect on inhibin or FSH concentrations but resulted in acute inhibition (P<0·01) of ovarian oestradiol, androstenedione and inhibin secretion, a delay (P<0·05) in the time to the LH surge and a depression (P<0·05) in luteal-phase progesterone concentrations. In conclusion, while the depression in FSH induced by rhlnh cannot be excluded as a cause for the inhibitory effects of rhInh treatment on ovarian function, such a mechanism cannot fully explain the ovarian responses obtained to rhInh infusion. These results therefore support a direct ovarian role for inhibin in the modulation of ovarian function in addition to its indirect role in controlling FSH. This conclusion is supported by the demonstration that bFF can induce similar inhibitory effects on ovarian function without changing FSH. Journal of Endocrinology (1996) 149, 531–540


1990 ◽  
Vol 126 (3) ◽  
pp. 377-384 ◽  
Author(s):  
B. K. Campbell ◽  
A. S. McNeilly ◽  
H. M. Picton ◽  
D. T. Baird

ABSTRACT By selective removal and replacement of LH stimulation we sought to examine the relative importance of inhibin and oestradiol in controlling FSH secretion, and the role of LH in the control of ovarian hormone secretion, during the follicular phase of the oestrous cycle. Eight Finn–Merino ewes which had one ovary removed and the other autotransplanted to a site in the neck were given two injections of a gonadotrophin-releasing hormone (GnRH) antagonist (50 μg/kg s.c.) in the follicular phase of the cycle 27 h and 51 h after luteal regression had been induced by cloprostenol (100 μg i.m.). Four of the ewes received, in addition, i.v. injections of 2·5 μg LH at hourly intervals for 23 h from 42 to 65 h after GnRH antagonist treatment. Ovarian jugular venous blood samples were taken at 10-min intervals for 3 h before and 5 h after the injection of antagonist (24–32 h after cloprostenol) and from 49 to 53 h after antagonist (74–78 h after cloprostenol). Additional blood samples were taken at 4-h intervals between the periods of intensive blood sampling. The GnRH antagonist completely inhibited endogenous pulsatile LH secretion within 1 h of injection. This resulted in a marked decrease in the ovarian secretion of oestradiol and androstenedione (P<0·001), an effect that was reversible by injection of exogenous pulses of LH (P<0·001). The pattern of ovarian inhibin secretion was episodic, but removal or replacement of stimulation by LH had no effect on the pattern or level of inhibin secretion. Peripheral concentrations of FSH rose (P<0·01) within 20 h of administration of the antagonist and these increased levels were maintained in ewes given no exogenous LH. In ewes given LH, however, FSH levels declined within 4 h of the first LH injection and by the end of the experimental period the levels of FSH were similar to those before administration of antagonist (P<0·01). These results confirm that ovarian oestradiol and androstenedione secretion, but not inhibin secretion, is under the acute control of LH. We conclude that oestradiol, and not inhibin, is the major component of the inhibitory feedback loop controlling the pattern of FSH secretion during the follicular phase of the oestrous cycle in ewes. Journal of Endocrinology (1990) 126, 377–384


1976 ◽  
Vol 71 (1) ◽  
pp. 77-85 ◽  
Author(s):  
K. P. McNATTY ◽  
D. T. BAIRD ◽  
A. BOLTON ◽  
P. CHAMBERS ◽  
C. S. CORKER ◽  
...  

SUMMARY The concentrations of androstenedione, testosterone, oestrone and oestradiol-17β were measured in peripheral and ovarian venous blood and follicular fluid of women at various stages of the menstrual cycle. The concentration of oestradiol was similar in small follicles (diameter < 8 mm) at all stages of the menstrual cycle and in large follicles (diameter ⩾ 8 mm) except during the mid- and late follicular phase when the concentration reached a peak (∼ 1500 ng/ml). The concentration of androstenedione was lowest in large preovulatory follicles at mid-cycle at a time when the secretion into the ovarian vein was markedly increased. The concentration of testosterone in large follicles (⩾ 8 mm) was unchanged during the follicular phase whereas in small follicles there was a peak at mid-cycle. The rise in the concentration of testosterone and androstenedione at mid-cycle in peripheral plasma may be due to increased secretion by the preovulatory follicle into the ovarian vein. It is suggested that the relatively low concentration of androstenedione in follicular fluid of the preovulatory follicle arises from increased aromatization by granulosa cells in the course of oestrogen synthesis.


1994 ◽  
Vol 143 (1) ◽  
pp. 13-24 ◽  
Author(s):  
B K Campbell ◽  
B M Gordon ◽  
R J Scaramuzzi

Abstract Transforming growth factor α (TGFα) inhibits hormone production by cultured follicular cells but evidence of an effect of TGFα on ovarian hormone secretion in vivo is still required. Eleven ewes with an autotransplanted ovary received, by ovarian arterial infusion, either 5 μg/h recombinant rat TGFα (n=6) or placebo (n=5) for 12 h on day 10 of the luteal phase. Two hours before the start and 1 hour before the end of the infusion each ewe received a single injection of gonadotrophin-releasing hormone (GnRH; 150 ng i.v.). Two hours after the end of the infusion luteal regression was induced with prostaglandin F2α (PGF2α; 125 μg i.m.). Ovarian and jugular venous blood samples were taken at 10-min, 15-min or 4-h intervals from 2 h before the start of the infusion until 96 h after PGF2α and the rates of secretion of ovarian oestradiol, inhibin, progesterone and androstenedione were determined. Jugular venous concentrations of LH and FSH were also measured and follicle populations monitored by real-time ultrasound scanning. Infusion of TGFα resulted in a significant (P<0.05) depression in the amplitude of the pulsatile response of oestradiol and androstenedione secretion to the GnRH-induced LH pulse at the end of the infusion. Ovarian inhibin secretion was acutely suppressed by TGFα infusion (P<0·001) and remained lower than controls for the period of the experiment. Luteal phase progesterone secretion was also acutely inhibited (P<0·001) by infusion of TGFα and in one treated ewe progesterone secretion was elevated 48–84 h after PGF2α. Jugular venous concentrations of FSH in TGFα-treated ewes were significantly (P<0·001) elevated over controls during the first 48 h of the follicular phase and the LH surge was delayed for about 10 h (P<0·05). Infusion of TGFα caused a marked decline (P<0·05) in the number of large follicles within 12 h of the end of the infusion. Two of the six treated ewes, including the one with high follicular phase progesterone, had unusually large (8·7 and 10 mm) follicles present from 48–96 h after PGF2α. We conclude that direct arterial infusion of TGFα results in acute inhibition of ovarian steroid and inhibin secretion that is associated with induction of atresia in the population of large follicles. The lack of feedback of ovarian hormones results in a rebound increase of FSH which stimulates the growth of more ovarian follicles and the eventual re-establishment of ovarian hormone secretion and normal cyclicity. Journal of Endocrinology (1994) 143, 13–24


Reproduction ◽  
1991 ◽  
Vol 93 (1) ◽  
pp. 81-96 ◽  
Author(s):  
B. K. Campbell ◽  
H. M. Picton ◽  
G. E. Mann ◽  
A. S. McNeilly ◽  
D. T. Baird

1990 ◽  
Vol 125 (3) ◽  
pp. 417-424 ◽  
Author(s):  
G. E. Mann ◽  
B. K. Campbell ◽  
A. S. McNeilly ◽  
D. T. Baird

ABSTRACT Passive immunization was used to investigate the importance of inhibin and oestradiol in the control of FSH production during the follicular phase of the oestrous cycle in the sheep. Four groups of five mature Scottish Blackface ewes were injected with normal sheep plasma (control), antiserum to the 1–26α peptide fragment of porcine inhibin, antiserum to oestradiol-17β, or a combination of the two antisera, 24 h following cloprostenol-induced luteal regression. There was no difference in the concentration of LH in jugular venous plasma between the control and inhibin-immunized groups following the injection of normal sheep plasma or inhibin antiserum, with both groups exhibiting normal LH surges. In both the groups immunized against oestradiol, the basal concentration of LH rose by 25–30% (P<0.05) during the 96-h period following injection, while the LH surge and consequent formation of a corpus luteum was inhibited. In all three immunized groups there was a significant (P<0.001) rise in the concentration of FSH starting 3.8–4.8 h after the injection of antiserum. The duration of the rise was similar in the groups injected with oestradiol antiserum alone (43.6±12.8 h) or in combination with inhibin antiserum (40.6 ± 11.7 h), but was significantly (P<0.05) shorter in the group immunized against inhibin alone (17.0 ± 0.5 h). The rise in FSH was similar in the groups immunized against inhibin (142 ± 6%) or oestradiol (143±4%) alone, and was significantly (P<0.01) greater in the group injected with both antisera (195± 17%). These results provide evidence that both oestradiol and inhibin play a role in regulating the concentration of FSH during the follicular phase of the oestrous cycle, while reinforcing the hypothesis that inhibin is not involved in the regulation of LH production. Journal of Endocrinology (1990) 125, 417–424


1975 ◽  
Vol 64 (3) ◽  
pp. 555-571 ◽  
Author(s):  
K. P. McNATTY ◽  
W. M. HUNTER ◽  
A. S. McNEILLY ◽  
R. S. SAWERS

SUMMARY The concentrations of FSH, LH, prolactin, oestradiol and progesterone were measured in peripheral plasma and follicular fluid of women throughout the menstrual cycle. With the exception of prolactin, concentrations of pituitary and steroid hormones in follicular fluid correlated with those in peripheral plasma. Follicle-stimulating hormone was present in a greater number of small follicles ( < 8 mm) during or just after the peaks of FSH in peripheral plasma. During the mid-follicular phase the concentration of both FSH and oestradiol in fluid from large follicles ( ≥ 8 mm) was high. During the late follicular phase the large follicles ( ≥ 8 mm) contained high amounts of progesterone in addition to oestradiol, low physiological levels of prolactin, and concentrations of LH and FSH about 30 and 60% respectively of those found in plasma. By contrast no large 'active' follicles ( ≥ 8 mm) were found during the luteal phase although many contained both LH and FSH. Luteinizing hormone was present in a proportion of small follicles ( < 8 mm) during the late follicular and early luteal but not at other stages of the menstrual cycle. It is suggested that a precise sequence of hormonal changes occur within the microenvironment of the developing Graafian follicle; the order in which they occur may be of considerable importance for the growth of that follicle and secretory activity of the granulosa cells both before and after ovulation.


1986 ◽  
Vol 110 (3) ◽  
pp. 507-510 ◽  
Author(s):  
T. Sawada

ABSTRACT Differences in the secretion of pregnane compounds by follicular polycystic ovaries of androgen-sterilized rats and by normal preovulatory ovaries of early prooestrous rats were compared. Some rats were injected i.v. with LH 30 min before bleeding, in order to stimulate the secretion of steroids. This injection of LH greatly increased the secretion of progesterone, 5α-pregnane-3,20-dione and 3α-hydroxy-5α-pregnan-20-one by both types of ovaries. The response of the two progesterone metabolites in the polycystic ovaries was low, suggesting low 5α-reductase activity. Because it is known that the preovulatory LH surge is absent in androgen-sterilized rats, a classical approach was taken to circumvent the probable deficit in cyclic release of LH by giving an i.v. injection of LH (25 μg) every 4 days for 16 days. Ovarian venous blood was collected 4 days after the last injection. The mean secretion of 5α-pregnane-3,20-dione and 3α-hydroxy-5α-pregnan-20-one from the ovaries of such androgen-sterilized rats became much (P <0·01) higher than that of multiple saline-treated controls. These results suggest that low 5α-reductase activity of polycystic ovaries in androgen-sterilized rats may be due to the absence of cyclic release of LH from the pituitary gland. J. Endocr. (1986) 110, 507–510


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