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1.
Science ; 218(4573): 700-2, 1982 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-6890235

RESUMO

When ethanol was administered intravenously to pregnant monkeys, a transient but marked collapse of umbilical vasculature was observed uniformly within about 15 minutes. The ethanol-induced impairment of umbilical circulation produced severe hypoxia and acidosis in the fetus; recovery occurred during the succeeding hour. This striking interruption of feto-placental circulation may explain one of the mechanisms of mental retardation, a frequent manifestation in children afflicted with fetal alcohol syndrome.


Assuntos
Etanol/farmacologia , Transtornos do Espectro Alcoólico Fetal/etiologia , Sofrimento Fetal/induzido quimicamente , Prenhez/efeitos dos fármacos , Cordão Umbilical/efeitos dos fármacos , Acetaldeído/sangue , Animais , Modelos Animais de Doenças , Etanol/sangue , Feminino , Macaca fascicularis , Macaca mulatta , Gravidez
2.
Science ; 222(4630): 1353-5, 1983 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-6318312

RESUMO

Endotoxin-free thymosin fraction 5 elevated corticotropin, beta-endorphin, and cortisol in a dose- and time-dependent fashion when administered intravenously to prepubertal cynomolgus monkeys. Two synthetic component peptides of thymosin fraction 5 had no acute effects on pituitary function, suggesting that some other peptides in thymosin fraction 5 were responsible for its corticotropin-releasing activity. In agreement with these observations, total thymectomy of juvenile macaques was associated with decreases in plasma cortisol, corticotropin, and beta-endorphin. These findings indicate that the prepubertal primate thymus contains corticotropin-releasing activity that may contribute to a physiological immunoregulatory circuit between the developing immunological and pituitary-adrenal systems.


Assuntos
Hormônio Adrenocorticotrópico/sangue , Timosina/farmacologia , Timo/fisiologia , Animais , Relação Dose-Resposta a Droga , Endorfinas/sangue , Feminino , Hidrocortisona/sangue , Cinética , Macaca fascicularis , Timalfasina , Timectomia , Timosina/análogos & derivados , beta-Endorfina
3.
J Clin Invest ; 64(4): 1070-3, 1979 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-225351

RESUMO

The testicular luteinizing hormone (LH) receptors of the rhesus monkey and human have many features in common, including high equilibrium association constant, marked species specificity, and relatively low binding capacity. We have, therefore, used rhesus monkeys as models for human LH-receptor regulation in vivo during gonadotropin treatment. In four adult male monkeys, treated with 10,000 IU human chorionic gonadotropin (hCG), serum and testicular steroidogenic responses were monitored at 24-h intervals during the following 4 d, and LH-receptor concentrations were measured by (125)I-hCG binding to 15,000-g particles prepared from testis biopsy specimens. In treated animals, serum hCG was maximal on day 1 at 322+/-16 ng/ml and declined to 24.4+/-2.3 ng/ml by day 4. Serum testosterone was increased threefold during the subsequent 4 d (from 6.5+/-2.0 to 18.6+/-4.4 ng/ml) but serum progesterone remained unchanged. In contrast, serum 17alpha-hydroxyprogesterone increased 12-fold to 5.5+/-0.5 ng/ml at day 1 and was increased fourfold during the subsequent 3 d. The LH-receptor binding capacity of the primate testis was reduced by 18.3+/-6.0% on day 1, 51.7+/-7.4% on day 2, and 45.3+/-2.4% on day 4. Occupancy of the LH receptors by endogenously bound hCG was significant on day 1 but was negligible by day 4. These data demonstrate that gonadotropin-induced LH-receptor depletion occurs in the rhesus testis and indicate that primate gonadotropin receptors are susceptible to the regulatory processes recently described in the rat. In addition, the simultaneous and disproportionate accumulation of 17alpha-hydroxyprogesterone indicates that 17,20-desmolase was rate-limiting under these conditions in the primate testis Leydig cell.


Assuntos
Gonadotropina Coriônica/farmacologia , Hormônio Luteinizante/metabolismo , Macaca mulatta/metabolismo , Macaca/metabolismo , Receptores de Superfície Celular/metabolismo , Testículo/metabolismo , Animais , Haplorrinos , Células Intersticiais do Testículo/metabolismo , Masculino , Progesterona/sangue , Testosterona/sangue
4.
J Clin Invest ; 58(5): 1061-8, 1976 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-825531

RESUMO

Androgen-binding protein (ABP) has been found in the cytosol of testicular and epididymal homogenates of several sub-primate species. In those species which had the plasma androgen binding protein, testosterone-estradiol-binding globulin (TeBG), ABP and TeBG were found to be physically similar. We investigated the possibility that ABP might exist in monkey and man using the cytosol of testicular and epididymal homogenates and aspirates obtained by direct micropuncture of the rete testis. In polyacrylamide gel electrophoresis, pH 7.8, testicular and epididymal cytosols of monkey and man were found to contain several binding proteins of different size and net charge that bind dihydrotestosterone. These binding proteins were either indistinguishable from TeBG or could be related to TeBG as size and/or charge isomers. No ABP was detectable in up to 200 mul of monkey rete testis fluid obtained by direct micropuncture, though ABP is detectable in as little as 5 mul of rat rete testis fluid. The data suggest that the ABP's detected in the testicular and epididymal cytosols in monkey and man represent isomeric forms of plasma TeBG, and their presence in testicular cytosol most likely derives from blood contamination.


Assuntos
Androgênios , Proteínas de Transporte , Epididimo/análise , Globulina de Ligação a Hormônio Sexual/análise , Testículo/análise , Animais , Di-Hidrotestosterona , Eletroforese em Gel de Poliacrilamida , Haplorrinos , Humanos , Focalização Isoelétrica , Macaca mulatta , Masculino , Globulina de Ligação a Hormônio Sexual/sangue
5.
Trends Endocrinol Metab ; 3(7): 259-63, 1992 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18407109

RESUMO

GnRH antagonists, unlike GnRH agonists, do not act via "downregulation." Instead, GnRH antagonists monopolize the GnRH receptors to such an extent that endogenous GnRH is unable to bind to sufficient numbers of GnRH receptors to provoke release of LH/FSH. This fundamental difference in the mechanism of action of GnRH antagonists versus GnRH agonists is anticipated to result in clinical benefits for certain applications.

6.
Endocrinology ; 127(1): 319-24, 1990 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-2193798

RESUMO

The metabolism of GnRH by membrane-bound and serum-degrading enzymes may play an important role in the regulation of pituitary gonadotropin secretion. We examined GnRH metabolism by pituitary cells in vitro and the metabolism of exogenously administered GnRH in vivo in the presence and absence of estradiol (E2) and progesterone (P4). Ovariectomized cynomolgus monkeys were implanted with E2- and/or P4-filled Silastic capsules to simulate the estrogen and progesterone patterns of the normal menstrual cycle. Peripheral levels of GnRH after a 1-microgram iv injection were highest in the E2-replaced monkeys. Peripheral GnRH levels reached a higher peak and remained in circulation longer in monkeys treated with E2-filled Silastic implants than in those treated with E2 plus P4 or nonsteroid-replaced ovariectomized monkeys. In agreement with the in vivo data, GnRH was rapidly metabolized by acutely dispersed cells isolated from pituitaries removed from nonsteroid-replaced ovariectomized monkeys. Priming with E2 followed by P4 in vivo attenuated the clearance of GnRH in vitro, and E2 treatment alone almost completely blocked the ability of pituitary cells to bind and/or degrade GnRH in vitro. In a parallel study, cells prepared from rat pituitaries removed on the morning of proestrus (when serum E2 is highest) metabolized GnRH in vitro more slowly than pituitary cells removed at estrus, diestrus, or metestrus. In summary, our data suggest that E2 inhibits GnRH metabolism by monkey and rat pituitary cells in vitro and exogenously administered GnRH in vivo. Although the precise mechanism of action of E2 is unknown, inhibition of membrane-bound and serum proteases seems likely. The action of E2 may be to increase GnRH presentation to the pituitary and enhance LH and FSH secretion under conditions where circulating levels of the hormone are elevated, such as at midcycle.


Assuntos
Estradiol/farmacologia , Hormônio Liberador de Gonadotropina/metabolismo , Adeno-Hipófise/metabolismo , Progesterona/farmacologia , Animais , Diestro/fisiologia , Estro/fisiologia , Feminino , Hipofisectomia , Cinética , Macaca fascicularis , Metestro/fisiologia , Ovariectomia , Adeno-Hipófise/efeitos dos fármacos , Proestro/fisiologia , Ratos , Ratos Endogâmicos
7.
Endocrinology ; 104(2): 396-401, 1979 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-446368

RESUMO

A chemically synthesized Na-acetyl-triacontapeptide analogous to the carboxyl-terminal region (residues 116--145) of hCG beta-subunit was conjugated to bovine thyroglobulin. This synthetic antigen was used to immunize five rabbits; one of these rabbits (H-114) generated a useable antiserum. The binding properties of this antiserum were compared extensively to a well characterized antiserum (H-93) against the natural tricosaglycopeptide (residues 123--145) of desialylated hCG beta-subunit conjugated to bovine serum albumin. The two antisera showed nearly identical immunological specificities and sensitivities when examined in a conventional RIA system. These similarities included: 1) antibody recognition sites residing at the carboxyl-terminal pentadecapeptide region; 2) binding neither [125I]iodo-hLH nor [125I]iodo-oLH; and 3) lack of neutralizing capability against the biological activity of hCG in vivo. However, synthetic pentadeca or longer peptides are twice as potent in inhibiting 125I]iodo-hCG binding to H-114 than to H-93. Synthetic peptides may provide a superior means of generating antisera capable of distinguishing hCG from human LH, since they can be obtained more easily in large quantities than analogous purified natural fragments and because peptides of synthetic origin avoid the risk of contamination from strongly antigenic regions of the native molecules. Such hCG-specific antisera may have extensive application in RIA systems and fertility control, where selective binding to hCG but not human LH is desired.


Assuntos
Gonadotropina Coriônica/imunologia , Soros Imunes , Ligação Competitiva , Humanos , Substâncias Macromoleculares , Fragmentos de Peptídeos , Hipófise/análise , Radioimunoensaio , Ensaio Radioligante , Relação Estrutura-Atividade
8.
Endocrinology ; 105(1): 69-79, 1979 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-109289

RESUMO

This study was designed to examine effects of previous ovarian status on subsequent follicle growth and the role of between-ovary communication in the regulation of folliculogenesis and gonadotropin secretion during the primate ovarian cycle. Responses to luteectomy were compared in two groups of rhesus monkeys. In the first, follicle growth and corpus luteum function had been constrained chronically to a single ovary by hemiovariectomy performed 66--258 days earlier; the second group was composed of intact monkeys that underwent contralateral wedge resection at luteectomy. In each group, luteal ablation was followed by a prompt fall in serum progesterone levels, a premature onset of menses, and the next preovulatory gonadotropin surges 14.7 +/- 1.1 or 15.4 +/- 1.4 days later (mean +/- SE; P greater than 0.25). Although the patterns of circulating estradiol before and after ablation in each group were superimposable, luteectomy in monkeys lacking a contralateral ovary was followed by a large (2- to 4-fold) and prolonged (7--10 days) increase in serum FSH, whereas in monkeys with two ovaries, serum FSH levels exhibited only a small short-lived rise. The findings indicate that 1) prior chronic constraint of ovarian function to a single ovary did not alter the overall time course of new follicle growth culminating in ovulation after luteectomy; 2) the contralateral ovary provided the principal negative feedback regulation of gonadotropin secretion for some time after luteectomy even though it may not have been the exclusive site of new follicle growth; 3) whereas the ability of the luteectomized ovary to regulate tonic gonadotropin secretion was temporarily impaired, its ability to support the customary temporal pattern of follicle growth after luteal ablation was not; 4) some (contralateral) ovarian factor other than estradiol or progesterone apparently made a major contribution to the regulation of FSH secretion after luteectomy; and 5) folliculogenesis culminating in ovulation from a single follicle and the negative feedback regulation of tonic gonadotropin secretion in some circumstances may occur concurrently but separately on opposite ovaries or may occur at different times within the same ovary.


Assuntos
Corpo Lúteo/fisiologia , Hormônio Foliculoestimulante/metabolismo , Hormônio Luteinizante/metabolismo , Menstruação , Ovário/fisiologia , Animais , Castração , Corpo Lúteo/cirurgia , Feminino , Haplorrinos , Cinética , Macaca mulatta , Ovulação
9.
Endocrinology ; 128(4): 2036-40, 1991 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-1900784

RESUMO

The GnRH antagonist antide is among the most promising "third generation" compounds available for clinical evaluation. In primates, antide manifests prolonged (several weeks) and reversible inhibition of pituitary gonadotropin secretion after a single high dose injection. In the present study, we have examined the effects of antide on pituitary gonadotropin secretion in vitro. Dispersed anterior pituitary cells from adult female rats were plated (48 h; 5 x 10(5) cells/well), washed, and exposed to increasing concentrations of antide for up to 48 h. Media were removed, and cells were washed twice and then incubated with GnRH (1 x 10(-8) M) plus antide for 4 h. Media and cell lysates were assayed for LH/FSH by RIA. Antide had no effect on basal LH/FSH secretion at any dose tested (10(-6)-10(-12) M). In contrast, GnRH-stimulated LH/FSH secretion was inhibited by this GnRH antagonist in a dose- and time-dependent manner. When incubated simultaneously, antide blocked GnRH-stimulated gonadotropin secretion, with a maximal effect at 10(-6) M (ED50, 10(-7) M). Preincubation of pituitary cells with antide for 6-48 h before GnRH exposure shifted the dose-response curve to the left; the maximally effective dose was 10(-8) M; the ED50 was 10(-10) M antide after 48-h preincubation. Intracellular LH/FSH levels increased concomitant with the decrease in secreted gonadotropins. Total LH/FSH levels (secreted plus cell content) remained unchanged. The inhibition of LH secretion by antide was specific for GnRH-stimulated gonadotropin secretion; antide had no effect on K(+)-stimulated LH secretion. Moreover, antide had little or no residual effect on LH secretion; full recovery of GnRH responsiveness in vitro occurred within 4 h after removal of antide. Lineweaver-Burke analysis of antide inhibition of GnRH-stimulated LH secretion indicated that antide is a direct competitor of GnRH at the level of the pituitary GnRH receptor. In summary, antide is a pure antagonist of GnRH stimulation of gonadotropin secretion; no agonistic actions of antide were manifest in vitro. Moreover, antide has no apparent noxious or toxic effect on pituitary cells in culture; the actions of antide are immediately reversible upon removal of antide from pituitary gonadotropes. We conclude that the long term inhibition of gonadotropin secretion by antide in vivo is not due to deleterious effects of this compound at the level of the pituitary gonadotrope.


Assuntos
Hormônio Foliculoestimulante/metabolismo , Hormônio Liberador de Hormônio do Crescimento/antagonistas & inibidores , Hormônio Luteinizante/metabolismo , Oligopeptídeos/farmacologia , Adeno-Hipófise/metabolismo , Animais , Células Cultivadas , Feminino , Hormônio Liberador de Hormônio do Crescimento/farmacologia , Adeno-Hipófise/efeitos dos fármacos , Potássio/farmacologia , Ratos , Ratos Endogâmicos
10.
Endocrinology ; 96(3): 789-91, 1975 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-1116484

RESUMO

Concentrations of macaque chorionic gonadotropin (mCG) in placenta, blood and urine of rhesus monkeys have been measured by both radioimmunoassay and bioassay throughout gestation. mCG was easily detected and quantified in these specimens for a brief period in early pregnancy, but was not detectable between the 40th day of pregnancy and term in placental extracts, serum, or 40-fold urine concentrates. The apparent absence of mCG after the 40th day of pregnancy makes these macaques a valuable model for pregnancy research, where the absence of chorionic gonadotropin is experimentally desirable. Unlike women and some higher primates, the functional status of the fetal, placental and maternal endocrine compartments of macaques can be studied in the absence of circulating chorionic gonadotropin during mid and late gestation.


Assuntos
Gonadotropina Coriônica/metabolismo , Placenta/metabolismo , Animais , Bioensaio , Gonadotropina Coriônica/sangue , Gonadotropina Coriônica/urina , Feminino , Idade Gestacional , Macaca , Camundongos , Gravidez , Prenhez , Radioimunoensaio , Fatores de Tempo
11.
Endocrinology ; 103(6): 2112-8, 1978 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-155005

RESUMO

The concentrations of the adrenal steroids dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS), and delta 4-androstenedione (delta 4-A) have been measured by RIA before and after sexual maturation in plasma of rodents, domestic animals, and primates to determine whether these species exhibit and adrenarchal process comparable to man. The average concentrations of DHA and DHAS were less than 60 ng/dl and 5 microgram/dl, respectively, in plasma of sexually mature rodents and domestic animals, and a significant increase in the plasma DHA level after sexual maturation was seen only in the rabbit and dog. The concentrations of DHA, DHAS, and delta 4-A in 21 rhesus monekeys from 0-3 yr of age were 2021 +/- 235 ng/dl (mean +/- SE), 357 +/- 60 microgram/dl, and 107 +/- 9 ng/dl, respectively, and did not increase during sexual maturation. By contrast, DHA, DHAS, and delta 4-A levels in plasma of chimpanzees were 5.9-fold, 3.3-fold, and 4.8-fold greater, respectively, in 7- to 22-compared to 0- to 3-yr-old animals. Temporally, the increase in DHA levels in the chimpanzee is apparent at 5 yr and this precedes the increase in gonadal steroids, as is characteristic of human adrenarche. It is apparent that adrenal androgen levels and their developmental patterns differ markedly among species, and that among the species examined, only the chimpanzee exhibits an adrenarche comparable to that of man.


Assuntos
Glândulas Suprarrenais/fisiologia , Androstenodiona/sangue , Desidroepiandrosterona/sangue , Maturidade Sexual , Animais , Bovinos , Galinhas , Cricetinae , Cães , Feminino , Cabras , Cobaias , Haplorrinos , Cavalos , Masculino , Primatas , Coelhos , Ratos , Ovinos , Especificidade da Espécie , Suínos
12.
Endocrinology ; 128(4): 2041-4, 1991 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-1900785

RESUMO

Previous data from this laboratory revealed a rapid and unexpectedly long inhibition of pituitary gonadotropin secretion in ovariectomized monkeys after a single high dose injection of the GnRH antagonist antide. This extended action of antide may correlate with an extended presence of antide in the peripheral circulation. We have reported on use of a RRA for antide in serum; however, during such a prolonged presence in the body, the possibility of catabolic loss of biological activity remained to be analyzed. In the present study, we have developed an in vitro pituitary cell bioassay for antide to investigate the pharmacokinetics and possible mechanism(s) contributory to its long action. Dispersed anterior pituitary cells from adult female rats were plated (48 h; 5 x 10(5) cells/well), washed, and incubated with 0.024-6 ng antide for 24 h. Media were removed, and cells were washed twice and then incubated with GnRH (1 x 10(-8) M) plus antide standards or serum samples for 4 h. Before antide injection into long term ovariectomized monkeys, peripheral GnRH antagonist levels were undetectable. One day after a single injection (3.0 mg/kg, sc, in 50% propylene glycol-water), the level of antide was 31 +/- 13 ng/ml (n = 3). Thereafter, antide levels declined slowly and were still detectable (greater than 1.4 ng/ml) in two of three monkeys 31 days after injection. After iv administration (3.0 mg/kg; n = 2), peripheral antide levels followed a similar pharmacokinetic profile and declined slowly. Detectable antide concentrations were still present 36 days after single iv injection in both monkeys. The circulating half-lives of antide were 1.7 and 14.5 days for the first and second phases, respectively. Peripheral LH levels were suppressed to the limits of detectability within 1 day and slowly recovered to pretreatment levels within 30 +/- 5 days after sc or iv antide treatment. The ratio of bioactive antide to antide levels measured by RRA was similar throughout the study (chi = 1.24 +/- 0.09; range, 0.40-2.22), although there was a trend toward an increased B/R ratio at the end of the study. In summary, we have developed an in vitro bioassay using cultured rat pituitary cells to measure biologically active antide concentrations in peripheral circulation after sc and iv treatments. The prolonged action of antide on pituitary gonadotropin secretion in vivo is apparently due to the continued presence of biologically active antide in circulation after a single injection.(ABSTRACT TRUNCATED AT 400 WORDS)


Assuntos
Bioensaio , Hormônio Foliculoestimulante/metabolismo , Hormônio Liberador de Hormônio do Crescimento/antagonistas & inibidores , Hormônio Luteinizante/metabolismo , Oligopeptídeos/farmacologia , Adeno-Hipófise/metabolismo , Animais , Células Cultivadas , Feminino , Meia-Vida , Cinética , Macaca fascicularis , Oligopeptídeos/sangue , Oligopeptídeos/farmacocinética , Ovariectomia , Adeno-Hipófise/efeitos dos fármacos , Ensaio Radioligante , Ratos , Ratos Endogâmicos
13.
Endocrinology ; 107(1): 237-44, 1980 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-6769663

RESUMO

Blood samples were obtained frequently from stumptailed monkeys (Macaca arctoides) at midcycle and assayed for FSH, LH, 17 beta-estradiol, and progesterone. Periovulatory endocrine events were generally similar to those which have been described in rhesus monkeys and women. Although the midcycle patterns of estradiol in individual monkeys appeared quite varied, careful evaluation indicated the following general characteristics: 1) a plateau or transient decline in estradiol 30-44 h before the LH peak, 2) a sharp rise in serum estradiol before the initiation of the LH rise, 3) a diminution in serum concentrations or a decline in the rate of estradiol increase at the initiation of the LH rise, and 4) an elevation in estradiol at the time of the highest serum LH value. The first elevation in serum progesterone occurred 0-12 h before the LH peak and after the initiation of the LH surge. An unusual finding was a second midcycle rise in serum FSH, which occurred 2-3 days after the LH peak in 10 of 13 menstrual cycles. The biological significance of this second FSH rise in stumptailed monkeys is not known with certainty, but available evidence suggests that it enhances postovulatory progesterone and estrogen syntheses. Two methods are presented for the RIA of serum FSH in the stumptailed macaque.


Assuntos
Estradiol/sangue , Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Ovulação , Progesterona/sangue , Animais , Feminino , Haplorrinos , Cinética , Macaca , Radioimunoensaio
14.
Endocrinology ; 100(1): 155-61, 1977 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-401483

RESUMO

To identify factors regulating the initiation of follicle growth in adult primates, the ovarian cycle of sexually mature rhesus monkeys was interrupted by surgical ablation of the preovulatory follicle or functioning corpus luteum (CL). In 10 of 10 animals, cautery of the largest visible follicle on Day 8-12 of the cycle blocked ovulation, and in all but one abolished the expected midcycle surges of gonadotropin secretion. In 8 monkeys of this group, surges of LH and FSH release occurred 12.4 +/- 0.9 days (d) (mean +/- SE) after cautery, coincident with elevations in serum estrogens, and succeeded by typical luteal phase patterns of circulating progesterone (P). No gonadotropin or estrogen surges were observed during the next 32 days of sampling in the remaining pair, despite visible new vesicular follicles. Removal of the CL in 5 of 5 monkeys 4-6 days after the midcycle LH surge was followed by a reduction in serum P to less than 0.25 ng/ml within 24 h and by the onset of menses within 3-4 days. After luteectomy in 4 of the 5 animals, preoperative levels of LH and FSH were maintained until 12.8 +/- 0.9 days, when typical surges of gonadotropin secretion occurred, followed by a normal luteal phase pattern of P. The fifth luteectomized monkey menstruated again 25 days after ablation without intervening surges of estrogen or gonadotropin release and did not ovulate. Sham follicle cautery did not block ipsilaternal ovulation or impair progesterone secretion by the CL in 2 of 2 monkeys. These observations indicate that, by the middle of the follicular phase, the follicle destined to ovulate had been selected, and that no other follicles were soon competent to mature. That the interval from ablation, at either phase of the cycle, until the next ovulation was the same indicates: a) that the prevailing ovarian steroidal milieu at ablation had no discernible differential effect on the time-course of resumed ovarian activity, and b) that midcycle surges of estrogen or gonadotropin secretion were not required either to initiate or synchronize subsequent follicle growth.


Assuntos
Folículo Ovariano/citologia , Ovulação , Animais , Diferenciação Celular , Corpo Lúteo/fisiologia , Estrogênios/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Haplorrinos , Hormônio Luteinizante/sangue , Macaca mulatta , Menstruação , Folículo Ovariano/fisiologia , Progesterona/sangue
15.
Endocrinology ; 100(2): 506-12, 1977 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-401732

RESUMO

Progesterone production in vitro, in the presence and absence of exogenous gonadotropin, was examined in suspensions of luteal cells, isolated by collagenase digestion of rhesus monkeys corpus luteum at various stages of the menstrual cycle. Cells isolated during mid-luteal phase (days 15-19) of the cycle secreted progesterone for up to 6 h in vitro. Mid-luteal phase cells were responsive to physiologic concentrations of human chorionic gonadotropin (hCG), with progesterone production significantly (P less than 0.05) enhanced by as little as 0.1 ng hCG/ml. Maximal stimulation was obtained with 100 ng hCG/ml. Both macaque chorionic gonadotropin (mCG) and human luteinizing hormone (hLH) significantly (P less than 0.01) increased progesterone production, while human follicle stimulating hormone (hFSH) did not. Under control conditions, in the presence of nutrient medium alone (no exogenous gonadotropin), the progesterone synthetic activity of mid-luteal phase cells was significantly (P less than 0.01) greater than that of cells from late luteal phase (days 22-28) of the cycle. Moreover, progesterone production by mid-luteal phase cells was consistently stimulated (P less than 0.01) by the presence of 100 ng hCG/ml, whereas late luteal phase cells were less sensitive or unresponsive to exogenous gonadotropin. The progesterone synthetic activity of luteal cells in vitro correlated positively with both the wet weight of the excised corpus luteum (r = 0.82, P less than 0.01) and the peripheral serum progesterone concentration immediately preceding luteectomy (r = 0.66, P less than 0.01). These findings suggest that freshly isolated luteal cells reflect the functional capability of the corpus luteum in vivo. It is apparent that the age of the rhesus monkey corpus luteum of the non-fertile menstrual cycle is an important factor governing luteal cell progesterone synthetic capability and luteal cell responsiveness to gonadotropin in vitro.


Assuntos
Gonadotropina Coriônica/farmacologia , Corpo Lúteo/metabolismo , Hormônio Foliculoestimulante/farmacologia , Hormônio Luteinizante/farmacologia , Menstruação/efeitos dos fármacos , Progesterona/metabolismo , Animais , Corpo Lúteo/efeitos dos fármacos , Feminino , Haplorrinos , Técnicas In Vitro , Cinética , Fase Luteal/efeitos dos fármacos , Macaca mulatta
16.
Endocrinology ; 100(6): 1557-65, 1977 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-404130

RESUMO

The concentration of biologically active LH in rhesus monkey (Macaca mulatta) serum was measured by a highly sensitive bioassay based upon testosterone production by dispersed rat interstitial cells. The sensitivity of the in vitro bioassay was equal to or higher than that of radioimmunoassay, with detection limits of 0.1 mIU of human menopausal gonadotropin (hMG) or 10 ng of a rhesus pituitary gonadotropin preparation (LER-1909-2). Parallel dose-response curves were obtained for hMG and rhesus monkey pituitary gonadotropin. The method permits bioassy of LH in 20-100 micronl of serum from adult male monkeys, and from female monkeys during the follicular and luteal phases of the menstrual cycle. Bioactive LH concentrations could be assayed in 0.25 to 5 micronl of serum from mid-cycle, postmenopausal, and castrated female monkeys. Serum LH was undetectable in two hypophysectomized adult female monkeys and six intact immature animals, and was 13+/-6 (SD) mIU/ml in adult male monkeys. In adult females, follicular phase LH levels ranged from 17 to 169 mIU/ml, with a mean of 76+/-52 mIU/ml. The midcycle LH peak was 1738+/-742 mIU/ml and the luteal phase values ranged from 6-47 mIU/ml, with a mean of 35+/-5 mIU/ml. Serum LH concentrations ranged from 100 to 900 mIU/ml in two menopausal females, and from 590-1480 mIU/ml in castrated females. Treatment of castrated female monkeys with estrogen plus progesterone produced an initial two-fold rise in serum LH within 3 days, followed by a gradual decline to one-fourth to one-tenth of the initial levels after 10 days of treatment. Serum LH was suppressed to undetectable levels during the third week, and remained so for the duration of the 60-day treatment period. Bioactive serum LH levels were comparable to levels determined by radioimmunoassay during the follicular and luteal phases of the menstrual cycle, with increased bio-immunoratio at the midcycle peak. The concentrations of biologically active serum LH in rhesus monkeys were similar to those in the human female during the follicular and luteal phases of the menstrual cycle, and were higher at midcycle and after castration. Serum LH levels measured by the interstitial cell bioassay in the rhesus monkey showed appropriate physiological changes and responses to gonadal steroid administration. Furthermore, the bioassay did not detect the LH-like material measured by heterologous radioimmunoassay in the serum of hypophysectomized, immature and steroid-suppressed monkeys. Thus, the rat interstitial cell assay provides a sensitive and valid procedure for measurement of biologically active LH in the serum of these non-human primates.


Assuntos
Hormônio Luteinizante/sangue , Menstruação , Animais , Bioensaio , Castração , Relação Dose-Resposta a Droga , Estradiol/farmacologia , Feminino , Haplorrinos , Humanos , Hipofisectomia , Células Intersticiais do Testículo/efeitos dos fármacos , Células Intersticiais do Testículo/metabolismo , Hormônio Luteinizante/farmacologia , Macaca mulatta , Masculino , Menopausa , Menotropinas/farmacologia , Progesterona/farmacologia , Radioimunoensaio , Ratos , Testosterona/biossíntese
17.
Endocrinology ; 109(6): 2270-2, 1981 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-6796391

RESUMO

In the follicular phase of the menstrual cycle, pulsatile patterns of LH and FSH secretion in monkeys change during maturation of the dominant follicle. At the preovulatory surge, the most striking event is the prodigious elevations of bioassayable LH, rising up to 50-fold within 24 h. Principally, establishment of the surge is due to marked enhancement of the amplitude of LH secretory pulses. In contrast, LH and FSH measured by RIA enter, in parallel, the surge modes of secretion approximately 5 h later than bioassayable LH and rise more slowly; the B:I ratio may reach 10:1. This same disparity between bioassayable versus immunoassayable LH was induced in castrate monkeys under estrogen positive feedback stimulation. We conclude that the preovulatory estrogen surge promotes the secretion of an LH molecule(s) having enhanced biological activity.


Assuntos
Hormônio Foliculoestimulante/metabolismo , Hormônio Luteinizante/metabolismo , Folículo Ovariano/fisiologia , Adeno-Hipófise/metabolismo , Animais , Estradiol/sangue , Retroalimentação , Feminino , Hormônio Foliculoestimulante/sangue , Fase Folicular , Hormônio Luteinizante/sangue , Macaca fascicularis , Macaca mulatta , Progesterona/sangue
18.
Endocrinology ; 132(3): 1151-7, 1993 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7679971

RESUMO

The present study examined the effects of 17 beta-estradiol benzoate (E2B) on the hypothalamic (HT) and anterior pituitary (AP) content of GnRH precursor (pro-GnRH-GAP), GnRH, GnRH-associated peptide (GAP), and substance-P (SP) during the various phases of the E2B-induced LH surge in cynomolgus monkeys. Changes in GnRH and GnRH-associated peptide (GAP) at both hypothalamic and AP levels were closely related at all times after E2B treatment. However, the pattern of change in the AP was very different from that in the HT. In the HT, pro-GnRH-GAP levels did not change significantly throughout the experimental period. In the AP, the pro-GnRH-GAP increased 48 h post-E2B treatment, the time of initiation of the LH surge. An 8-fold increase in AP GnRH occurred 30 h post-E2B treatment. There were no significant changes in the HT content of SP at any time after E2B treatment. However, there was a depletion of AP content by 48 h post-E2B, the time of the LH surge. These results demonstrate that E2 activates and deactivates in a coordinated manner the GnRH and SP systems of the HT-AP complex during initiation of the E2-induced LH surge. The observation that more significant changes occur in the AP than in the HT suggests that an important component of the E2 effect in inducing the LH surge may be directly at the AP level. This action involves changes in the contents of GnRH and SP in the AP.


Assuntos
Estradiol/farmacologia , Hormônio Liberador de Gonadotropina/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Hormônio Luteinizante/metabolismo , Ovariectomia , Adeno-Hipófise/metabolismo , Substância P/metabolismo , Animais , Estradiol/análogos & derivados , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Foliculoestimulante/metabolismo , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Cinética , Hormônio Luteinizante/sangue , Macaca fascicularis , Adeno-Hipófise/efeitos dos fármacos , Prolactina/sangue , Prolactina/metabolismo , Precursores de Proteínas/metabolismo , Fatores de Tempo
19.
Endocrinology ; 99(1): 137-45, 1976 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-820545

RESUMO

A sensitive and specific radioimmunoassay system for macaque follicle-stimulating hormone (mFSH) was developed utilizing an antiserum (H-31) prepared in a rabbit against purified ovine FSH as the immunogen. Sera from castrated female, adult male, and juvenile rhesus monkeys, as well as urinary extracts from castrated rhesus and bonnet monkeys, were used to demonstrate parallelism with a standard of partially purified monkey pituitary gonadotropins (LER-M-907-D). An extract of baboon pituitary tissue also showed parallelism with the reference standard. A highly purified pituitary extract (WP-X-105-28), containing approximately 75% macaque luteinizing hormone (mLH) and 1% mFSH, was used to demonstrate the specificity of this mFSH assay system. Sera and urinary extracts obtained from hypophysectomized monkeys did not show cross-reactivity in the assay. Macaque chorionic gonadotropin (mCG) did not produce an inhibition curve in the assay, as determined from serum samples and urinary extracts collected from pregnant monkeys at the time of peak mCG secretion. Serum concentrations of mFSH were suppressed in ovariectomized monkeys by the administration of ethinyl estradiol for 3 days, but returned to near pretreatment values by 96 h after the last estradiol administration. The determination of serum mFSH concentrations in daily blood samples obtained from 20 rhesus monkeys throughout ovulatory menstrual cycles revealed a pattern similar to that previously reported for the rhesus monkey and the woman. The peak value of serum mFSH during the menstrual cycle coincided with the midcycle surge of mLH in each case. The gonadotropin peaks were preceded by increasing serum concentrations of estradiol and followed by rises in the serum concentrations of progesterone. The follicular phase of the menstrual cycle was characterized by continuously decreasing serum concentrations of mFSH, reaching a preovulatory nadir 48 h prior to the midcycle mFSH and mLH surges. Serum mFSH concentrations following the midcycle gonadotropin surges decreased progressively as serum progesterone concentrations increased and reached a plateau, and then increased during the last week of the menstrual cycle as corpus luteum function was waning. We have prepared a large pool of antiserum for distribution under the aegis of the Contraceptive Development Branch of the Center for Population Research, the National Institute of Child Health and Human Development.


Assuntos
Hormônio Foliculoestimulante/sangue , Macaca mulatta/sangue , Macaca/sangue , Radioimunoensaio , Animais , Estudos de Avaliação como Assunto , Feminino , Haplorrinos , Soros Imunes , Menstruação , Gravidez , Especificidade da Espécie
20.
J Clin Endocrinol Metab ; 43(5): 1009-14, 1976 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-825526

RESUMO

Human growth hormone (hGH) B can be transformed to its biologically more active isohormones C, D and E by limited proteolysis with plasmin in vitro, but the physiological significance of this observation is not known. The possible occurrence of such an "activation process" in peripheral tissues was investigated in the rhesus monkey. Radioiodinated hGH (B, C) or isolated hGH-B were injected intravenously into 4 rhesus monkeys and blood samples were drawn at frequent intervals. Analysis of circulating hGH was carried out by precipitation of hGH with trichloroacetic acid (TCA) and excess anti-hGH antibody, and by polyacrylamide gel electrophoresis followed by autoradiography. The metabolic clearance rate, based on TCA-precipitable radioactivity, was 2.36 +/- 1.17 ml/min/kg (mean +/- SD), similar to that reported for man. No evidence for the presence of circulating hGH-D or E was found, although progressive accumulation of smaller radioactive fragments and free iodide was observed. It is concluded that peripheral tissues or plasma enzymes probably do not convert significant amounts of hGH-B or C to their more active charge isomers, at least in the monkey. Therefore, if enzymatic activation of hGH does occur in vivo, the pituitary gland would seem the most likely site for such a process.


Assuntos
Hormônio do Crescimento/metabolismo , Animais , Biotransformação , Feminino , Hormônio do Crescimento/sangue , Haplorrinos , Ponto Isoelétrico , Macaca mulatta , Masculino , Taxa de Depuração Metabólica , Relação Estrutura-Atividade
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