The Kainos Intact assay was the most sensitive, followed by the Immunotopics C-terminal assay. The findings of normal FGF23 concentrations in some patients with TIO may indicate that FGF 23 is not responsible for the hypophosphatemia in these patients or that FGF23 secretion by some tumors is partially responsive to serum phosphate. Normal FGF23 concentrations should be interpreted in relation to the serum phosphate and 1,25-dihydryxyvitamin-D concentrations.

Previous results have shown that the pattern of GnRH pulses (amplitude and frequency) can differentially regulate expression of gonadotropin subunit cytoplasmic messenger RNA (mRNA) concentrations. The present study examined the effect of GnRH pulses on alpha, LH-beta and FSH-beta transcription rates as determined by nuclear runoff transcription assay. GnRH pulses (saline to controls) were given to castrate, testosterone-replaced male rats, and the rate of subunit gene transcription was measured in isolated pituitary nuclei. The effect of GnRH treatment duration was examined by giving GnRH pulses (25 ng/pulse at 30-min intervals) for 1, 4, or 24 h. The basal transcription rates [expressed as parts per million (ppm)] were 82 +/- 25 for alpha; 39 +/- 19 for LH-beta and 27 +/- 6 ppm for FSH-beta, and transcription rates of all 3 subunits were elevated at 1 h (3-5-fold vs. saline controls). After 4 h of GnRH pulses, alpha and FSH-beta transcription rates were reduced vs. 1 h, but LH-beta mRNA synthesis rate was maintained. At 24 h, the alpha transcription rate was still increased (66%), but LH-beta and FSH-beta transcription rates had fallen to basal levels despite the continuing pulsatile GnRH stimulus. The second experiment investigated the effect of the duration of GnRH pulses (25 ng/pulse, every 30 min for 4 h or 24 h), on cytoplasmic subunit mRNA concentrations to assess if the initial 4-h increase in transcription rate would induce a rise in cytoplasmic mRNAs. After 4 h of GnRH pulses, alpha and LH-beta mRNAs were unchanged, but FSH-beta mRNA had increased by 36% (P less than 0.05) compared to controls. All 3 subunit mRNAs were increased (approximately 2-fold) by 24 h of GnRH pulses. Administering GnRH pulses for 4 h followed by 20 h of saline pulses did not increase alpha mRNA; LH-beta was slightly increased (P less than 0.05), but FSH-beta mRNA concentrations were similar to levels seen after 24 h of continued GnRH pulses. The third experiment examined the effects of a continuous GnRH infusion and different GnRH pulse frequencies on gonadotropin subunit transcription rates. GnRH (25 ng/pulse) was given at intervals of 8, 30, or 120 min for 4 h (saline to controls). The continuous GnRH infusion (200 ng/h) did not increase the transcription rate of any of the three subunit mRNAs. alpha-subunit transcription rate was increased 2.7- or 4-fold by GnRH pulses given every 8 or 30 min, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Reproductive function in mammals is regulated by the pituitary gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH). LH and FSH are secreted by the gonadotrope cell and act on the gonad in a sequential and synergistic manner to initiate sexual maturation and maintain cyclic reproductive function. The synthesis and secretion of LH and FSH are regulated mainly by the pulsatile release of the hypothalamic decapeptide hormone gonadotropin-releasing hormone (GnRH). The control of differential LH and FSH synthesis and secretion is complex and involves the interplay between the gonads, hypothalamus and pituitary. In this review, the transcriptional regulation of the gonadotropin subunit genes is discussed in a physiologic setting, and we aimed to examine the mechanisms that drive those changes.

The hypothalamic decapeptide GnRH is known to regulate the synthesis and secretion of LH and FSH by pituitary gonadotrope cells. The frequency of pulsatile GnRH secretion changes and LH and FSH are differentially secreted in various physiological situations. To investigate the potential role of altered frequency of GnRH stimulation in regulating differential secretion of LH and FSH, we examined the effects of GnRH frequency on expression of the alpha, LH beta, and FSH beta genes. GnRH pulses (25 ng/pulse) were administered to castrate testosterone-replaced rats at intervals of 8-480 min to cover the range of physiological pulsatile GnRH secretion. Fast frequency GnRH pulses (8-min pulse intervals) increased alpha-subunit mRNA concentrations 3-fold above those in saline-pulsed controls (controls, 1.01 fmol cDNA bound/100 micrograms pituitary DNA) and LH beta mRNA by 50% (controls, 0.18 fmol cDNA bound), but FSH beta mRNA was unchanged (controls, 0.38 fmol cDNA bound). GnRH pulses given every 30 min increased all three subunit mRNAs (alpha, 3-fold, LHbeta, 2-fold; FSH beta, 2-fold), and acute LH release and serum FSH concentrations were maximal after this frequency. Slower frequency GnRH stimuli (120- to 480-min pulse intervals) did not change alpha and LH beta mRNA levels, but increased FSH beta mRNA 2- to 2.5-fold, and FSH secretion was maintained. Equalization of the total dose of GnRH given at different intervals over 24 h confirmed the frequency dependence of subunit mRNA expression. Fast frequency GnRH stimuli (8 min) increased alpha mRNA 1.5- to 2.5-fold, while the same total GnRH doses were ineffective when given at slow frequency (480 min). Similarly, LH beta mRNA was only increased by GnRH pulses given at 8-min intervals. In contrast, FSH beta mRNA increased 2-fold after pulses given every 480 min, and the 8-min pulse interval was ineffective. The data show that the frequency of GnRH stimulation can differentially regulate gonadotropin subunit mRNA expression and may be a mechanism that enables a single GnRH peptide to selectively regulate gonadotropin subunit gene expression and hormone secretion.