Biomaterial Database

Differential regulation of luteinizing hormone, follicle-stimulating hormone, and free alpha-subunit secretion from the gonadotrope by gonadotropin-releasing hormone (GnRH): evidence from the use of two GnRH antagonists. 1990

J E Hall, and R W Whitcomb, and J E Rivier, and W W Vale, and W F Crowley

Reproductive Endocrine Unit, Massachusetts General Hospital, Boston 02114.

To examine the differential regulation of glycoprotein hormone secretion from the gonadotrope by GnRH, the Nal-Glu GnRH antagonist was administered to euthyroid women in the early follicular phase (days 1-5) of the menstrual cycle, and the results compared to previous studies with the Nal-Arg GnRH antagonist. After a 4-h period of baseline sampling at a frequency of every 10 min, a single sc dose of the GnRH antagonist was administered to each subject. Frequent sampling continued for 8 h, followed by hourly sampling for a further 16 h. LH, FSH, and free alpha-subunit were measured serially in assays with high specificity. There was a 90% concordance of LH and free alpha-subunit pulses during the baseline sampling period. Pulsatile secretion of LH and free alpha-subunit was immediately abolished at the highest dose of the Nal-Glu antagonist for at least 8 h. The maximum percent suppression of LH after administration of the Nal-Glu GnRH antagonist was 70 +/- 4%, 80 +/- 4%, and 83 +/- 1% at doses of 15, 50, and 150 micrograms/kg, respectively, compared to 51 +/- 10%, 70 +/- 5%, and 69 +/- 5% at doses of 50, 150, and 500 micrograms/kg Nal-Arg antagonist. Decreases in FSH were 28 +/- 2%, 32 +/- 7%, and 39 +/- 2%, with increasing doses of the Nal-Glu antagonist compared with 25 +/- 6%, 17 +/- 6%, and 28 +/- 4% reductions at increasing doses of the Nal-Arg antagonist. Free alpha-subunit decreased 22 +/- 4%, 23 +/- 4%, and 28 +/- 3% at increasing doses of the Nal-Glu antagonist and 12 +/- 4%, 27 +/- 4%, and 30 +/- 7% with increasing doses of the Nal-Arg antagonist. For the Nal-Glu antagonist, suppression of LH was greater than that of FSH and free alpha-subunit at all doses (P less than 0.001), while FSH suppression was greater than that of free alpha-subunit at the highest dose only (P less than 0.05). For the Nal-Arg antagonist, LH suppression was greater than that of FSH or free alpha-subunit at all doses (P greater than 0.01), and FSH suppression exceeded that of free alpha-subunit at the 50 micrograms/kg dose. Suppression of LH was greater with the Nal-Glu antagonist than with the Nal-Arg antagonist at doses of 50 and 150 micrograms/kg (P less than 0.05), and FSH suppression was greater with the Nal-Glu antagonist at 150 micrograms/kg (P less than 0.01), while the degrees of maximum suppression were similar for the two different GnRH antagonists for free alpha-subunit.(ABSTRACT TRUNCATED AT 400 WORDS)

UI	MeSH Term	Description	Entries
D007986	Luteinizing Hormone	A major gonadotropin secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Luteinizing hormone regulates steroid production by the interstitial cells of the TESTIS and the OVARY. The preovulatory LUTEINIZING HORMONE surge in females induces OVULATION, and subsequent LUTEINIZATION of the follicle. LUTEINIZING HORMONE consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH and FSH), but the beta subunit is unique and confers its biological specificity.	ICSH (Interstitial Cell Stimulating Hormone),Interstitial Cell-Stimulating Hormone,LH (Luteinizing Hormone),Lutropin,Luteoziman,Luteozyman,Hormone, Interstitial Cell-Stimulating,Hormone, Luteinizing,Interstitial Cell Stimulating Hormone
D007987	Gonadotropin-Releasing Hormone	A decapeptide that stimulates the synthesis and secretion of both pituitary gonadotropins, LUTEINIZING HORMONE and FOLLICLE STIMULATING HORMONE. GnRH is produced by neurons in the septum PREOPTIC AREA of the HYPOTHALAMUS and released into the pituitary portal blood, leading to stimulation of GONADOTROPHS in the ANTERIOR PITUITARY GLAND.	FSH-Releasing Hormone,GnRH,Gonadoliberin,Gonadorelin,LH-FSH Releasing Hormone,LHRH,Luliberin,Luteinizing Hormone-Releasing Hormone,Cystorelin,Dirigestran,Factrel,Gn-RH,Gonadorelin Acetate,Gonadorelin Hydrochloride,Kryptocur,LFRH,LH-RH,LH-Releasing Hormone,LHFSH Releasing Hormone,LHFSHRH,FSH Releasing Hormone,Gonadotropin Releasing Hormone,LH FSH Releasing Hormone,LH Releasing Hormone,Luteinizing Hormone Releasing Hormone,Releasing Hormone, LHFSH
D008597	Menstrual Cycle	The period from onset of one menstrual bleeding (MENSTRUATION) to the next in an ovulating woman or female primate. The menstrual cycle is regulated by endocrine interactions of the HYPOTHALAMUS; the PITUITARY GLAND; the ovaries; and the genital tract. The menstrual cycle is divided by OVULATION into two phases. Based on the endocrine status of the OVARY, there is a FOLLICULAR PHASE and a LUTEAL PHASE. Based on the response in the ENDOMETRIUM, the menstrual cycle is divided into a proliferative and a secretory phase.	Endometrial Cycle,Ovarian Cycle,Cycle, Endometrial,Cycle, Menstrual,Cycle, Ovarian,Cycles, Endometrial,Cycles, Menstrual,Cycles, Ovarian,Endometrial Cycles,Menstrual Cycles,Ovarian Cycles
D010060	Ovulation	The discharge of an OVUM from a rupturing follicle in the OVARY.	Ovulations
D010902	Pituitary Gland	A small, unpaired gland situated in the SELLA TURCICA. It is connected to the HYPOTHALAMUS by a short stalk which is called the INFUNDIBULUM.	Hypophysis,Hypothalamus, Infundibular,Infundibular Stalk,Infundibular Stem,Infundibulum (Hypophysis),Infundibulum, Hypophyseal,Pituitary Stalk,Hypophyseal Infundibulum,Hypophyseal Stalk,Hypophysis Cerebri,Infundibulum,Cerebri, Hypophysis,Cerebrus, Hypophysis,Gland, Pituitary,Glands, Pituitary,Hypophyseal Stalks,Hypophyses,Hypophysis Cerebrus,Infundibular Hypothalamus,Infundibular Stalks,Infundibulums,Pituitary Glands,Pituitary Stalks,Stalk, Hypophyseal,Stalk, Infundibular,Stalks, Hypophyseal,Stalks, Infundibular
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005260	Female		Females
D005498	Follicular Phase	The period of the MENSTRUAL CYCLE representing follicular growth, increase in ovarian estrogen (ESTROGENS) production, and epithelial proliferation of the ENDOMETRIUM. Follicular phase begins with the onset of MENSTRUATION and ends with OVULATION.	Menstrual Cycle, Follicular Phase,Menstrual Cycle, Proliferative Phase,Menstrual Proliferative Phase,Preovulatory Phase,Phase, Follicular,Phase, Menstrual Proliferative,Phase, Preovulatory,Proliferative Phase, Menstrual
D005640	Follicle Stimulating Hormone	A major gonadotropin secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Follicle-stimulating hormone stimulates GAMETOGENESIS and the supporting cells such as the ovarian GRANULOSA CELLS, the testicular SERTOLI CELLS, and LEYDIG CELLS. FSH consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity.	FSH (Follicle Stimulating Hormone),Follicle-Stimulating Hormone,Follitropin
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man