The Changing Ratio of Serum Bioactive to Immunoreactive Follicle-Stimulating Hormone in Normal Men Following Treatment With a Potent Gonadotropin Releasing Hormone Antagonist

Dahl, Kristine D.; Pavlou, Spyros N.; Kovacs, William J.; Hsueh, Aaron J. W.

doi:10.1210/jcem-63-3-792

Cited by 96 publications

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“…Discrepancies in FSH B/I ratios were also reported in pituitaries of rats under many endocrine states using in vivo and in vitro FSH bioassays (Diebel et al, 1973;Muchopadhyay et al, 1979;Chappel et al, 1983a;Chappel and Ramaley, 1985). Recently, FSH bioactivities in human serum have been analyzed with the present cultured granulosa cell assay (Dahl et al, 1986(Dahl et al, , 1987aTenover et al, 1987), or a cultured Sertoli cell assay (Padmanabhan et al, 1987).…”

Section: Discussionmentioning

confidence: 90%

“…Due to the lack of a sensitive and specific bioassay for FSH, no studies have measured serum bioactive FSH (bio-FSH) levels or compared ratios of bioactive to immunoreactive FSH (B/I) in prepubertal rats. Recently, a sensitive in vitro granulosa cell aromatase (GAB) bioassay for FSH was developed (Jia and Hsueh, 1985;Jia et al, 1986) and has proven useful in studying bioactive FSH levels of humans and gorillas in various endocrine states (Dahl et al, 1986(Dahl et al, , 1987a. The present study utilized the GAB assay to determine the bioactive FSH profiles in male and female rats from birth to Day 40 of age.…”

Section: Introductionmentioning

confidence: 99%

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Bioactive Follicle-Stimulating Hormone Levels in Serum and Urine of Male and Female Rats from Birth to Prepubertal Period1

Dahl

Jia

Hsueh

1988

Biology of Reproduction

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Using a sensitive in vitro granulosa cell aromatase bioassay (GAB), we determined serum and urinary levels of bioactive follicle-stimulating hormone (bio-FSH) in male and female rats from birth to Day 40 of age. In addition, serum immunoreactive FSH (immuno-FSH) was measured by radioimmunoassay to determine the bio- to immuno-(B/I) ratio of FSH. During the neonatal period (Days 1-7 of age), both sexes had detectable serum bio-FSH levels. In the infantile period (Days 7-21), serum bio-FSH levels initially decreased at Day 10 for both sexes, and then rose steadily, reaching maximum concentrations at Day 14 (males: 68.7 ng/ml; females: 114.6 ng/ml). Subsequently, FSH levels in the females decreased from Day 16 throughout the juvenile (Days 21-35) and prepubertal (Days 35-40) periods. In contrast, FSH levels in the males fluctuated during these periods. In the males, immuno-FSH reflected the bioactive profiles, with a B/I ratio of 2.2 +/- 0.2. In the females, the B/I ratio was approximately 2.5 during the neonatal and infantile periods but declined to approximately 1.0 during the juvenile and prepubertal periods, consistent with earlier observations of heterogeneous forms of pituitary FSH in immature female rats. Morning urine samples were also collected daily and bio-FSH concentrations were determined. In both sexes, urinary bio-FSH profiles were highly correlated (r = 0.93) with serum FSH throughout development. However, the urine concentrations were about 50-fold higher than serum.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Bioactive Follicle-Stimulating Hormone Levels in Serum and Urine of Male and Female Rats from Birth to Prepubertal Period1

Dahl

Jia

Hsueh

1988

Biology of Reproduction

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“…In addition, the differing degrees of suppression of LH and FSH may arise as a result of differential suppression of bioactive vs. immunoactive hormone by the antagonist. Bioactive FSH concentrations, determined by a granulosa cell aromatase bioassay (27), declined to a greater degree than immunoactive FSH in men receiving detirelix (28) and in hypogonadal women and women in the midfollicular phase receiving the 4F antagonist (29).…”

Section: Discussionmentioning

confidence: 93%

Inhibition of Follicular Development by a Potent Antagonistic Analog of Gonadotropin-Releasing Hormone (Detirelix)*

Marshall

Fluker

Jaffe

et al. 1991

The Journal of Clinical Endocrinology & Metabolism

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The ability of a potent long-acting antagonistic analog of GnRH to suppress gonadotropin secretion, disrupt follicular development, and inhibit ovulation was studied in six women with normal menstrual cycles. The GnRH antagonist detirelix ([N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Trp3,D-hArg(Et2)6,D-Ala10++ +] GnRH; Syntex Research) was administered to six women by sc injection on alternate days during a 27-day period. Six additional women underwent blood sampling only, without receiving detirelix. Within 8 h after the initial injection of detirelix, mean (+/- SEM) serum LH and FSH concentrations decreased by 74 +/- 2% and 26 +/- 3%, respectively. Mean immunoreactive FSH levels, however, returned to baseline after the first 72 h despite continued administration of detirelix. Mean estradiol (E2) concentrations decreased from 165 +/- 15 to 70 +/- 11 pmol/L in the first 24 h. During the treatment period follicular development was inhibited, and none of the six volunteers showed evidence of ovulation, as assessed by serum progesterone (P) levels. Maximal suppression of serum LH and E2 was observed approximately 24 h after each injection of detirelix. Compared to the control volunteers, those receiving detirelix had significantly lower mean serum LH (P less than 0.001), E2 (P less than 0.001), and P (P less than 0.001) levels during treatment; mean FSH concentrations, however, were not statistically different in the treatment and control groups. Rapid recovery of pituitary-ovarian function occurred after completion of treatment. In all six volunteers receiving detirelix, a LH surge occurred 10-16 days after the final injection, followed by increased P levels (greater than 32 nmol/L), indicating ovulation and a luteal phase of normal duration (12-14 days). Detirelix injections elicited local skin reactions (erythema and pruritus), but no systemic side-effects were observed. Thus, this long-acting GnRH antagonist can rapidly suppress gonadotropin secretion, inhibit follicular development, and prevent ovulation.

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“…These observations support the contention that FSH secretion may be less dependent on GnRH than LH, utilizing evidence that GnRH antagonists in vivo lower serum LH more than FSH, whether given to gonadectomized rats or intact rats at metestrus and proestrus [23,24]. In dispersed cell cultures the effect of Antag on LH and FSH is equal when given against a back ground of GnRH stimulation [8], but others have seen discre pancies using pituitary fragments [10], A GnRH antagonist si milar to the one used in the present experiments causes a drop in bioassayable FSH when given to male patients [25], while immunoassayable FSH shows the minor drop we have seen in rats [8,23]. Since we did not measure bioassayable FSH we do not know whether the differences in FSH:LH ratios seen in this study as a function of Antag are partly due to failure of the RIA to pick up changes in bioactive FSH.…”

Section: Discussionmentioning

confidence: 72%

Suppression of Basal and GnRH-Stimulated Gonadotropin Secretion Rate in vitro by GnRH Antagonist: Differential Effects on Metestrous and Proestrous Pituitaries

Hiatt¹,

Schwartz²

1989

Neuroendocrinology

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LH and FSH basal secretion rates (BSR) in vitro of pituitary fragments from female rats at metestrus or following ovariectomy parallel changes seen in serum gonadotropins. These findings led us to suspect that in vitro BSR of fragments depended on prior exposure to GnRH or lingering GnRH in the culture. We compared pituitaries removed from rats in two cycle stages, proestrus (PRO) and metestrus (MET). Rats were given a single injection of a potent GnRH antagonist, Antag – WY 45760 -[Ac-β(2)-D-Nal¹, 4-F-D-Phe², D-Trp³, D-Arg⁶]-LHRH, or oil prior to sacrifice at 09.00 h on PRO or MET. Pituitary fragments were perifused for 8 h. To test the effects of Antag in vitro some pituitaries from oil-injected rats were perifused with medium containing 1 µM Antag for the first 4 h. Starting at 5 hall chambers received hourly 10-min pulses of 1 µM GnRH. In PRO rats Antag injection in vivo lowered LH BSR to 50% and FSH to 70% of oil-treated controls. Surprisingly, Antag administered in vitro suppressed LH BSR to 30% and FSH to 55% of controls. In pituitaries from MET rats, BSR of LH and FSH were 20 and 70% of control PRO values and were unaffected by Antag treatment in vivo or in vitro. In PRO pituitaries LH and FSH responses to the first GnRH pulse were blunted by Antag in vivo but responses to subsequent pulses were unaffected; MET responses were not different from controls. In vitro Antag suppressed GnRH-stimulated release to 10–20% of controls at both cycle stages. The lower effectiveness of Antag in suppressing FSH has not been shown previously in vitro, but is consistent with in vivo studies in this laboratory. The relative ineffectiveness of the Antag in lowering BSR in MET compared to PRO pituitary fragments suggests that there is less GnRH present, consonant with data showing lower in vivo GnRH release and pituitary receptor levels in MET rats. Our findings suggest that pituitary fragments retain an appreciable amount of endogenous GnRH that stimulates apparent ‘basal’ gonadotropin secretion and that the concept of basal in vitro secretion rate in fragments needs reexamination.

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The Changing Ratio of Serum Bioactive to Immunoreactive Follicle-Stimulating Hormone in Normal Men Following Treatment With a Potent Gonadotropin Releasing Hormone Antagonist

Cited by 96 publications

References 0 publications

Bioactive Follicle-Stimulating Hormone Levels in Serum and Urine of Male and Female Rats from Birth to Prepubertal Period1

Bioactive Follicle-Stimulating Hormone Levels in Serum and Urine of Male and Female Rats from Birth to Prepubertal Period1

Inhibition of Follicular Development by a Potent Antagonistic Analog of Gonadotropin-Releasing Hormone (Detirelix)*

Suppression of Basal and GnRH-Stimulated Gonadotropin Secretion Rate in vitro by GnRH Antagonist: Differential Effects on Metestrous and Proestrous Pituitaries

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