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D L Hess

Publications and source records attributed to D L Hess.

At least 109 records · Page 6Linked to original sources

Inhibition of aromatization stimulates luteinizing hormone and testosterone secretion in adult male rhesus monkeys.

Experiments were conducted to examine the role of aromatization in the control of LH and testosterone secretion in adult male rhesus monkeys. Treatment of male monkeys (n = 7) with sc Silastic packets containing the aromatase inhibitor 1,4,6-androstatriene-3,17-dione (ATD) resulted in 1.5- to 3-fold elevations in serum LH and testosterone concentrations in six of seven animals. Concurrent treatment of ATD-treated monkeys with small quantities of estradiol-17 beta (n = 4) abolished the stimulatory effect of ATD. During ATD treatment, peripheral estradiol levels were reduced by 30% and hypothalamic aromatase activity, as determined in vitro, was reduced 80-90%. The lack of androgenic or antiandrogenic activity of ATD was demonstrated by its inactivity in either a mouse seminal vesicle bioassay or a highly sensitive penile spine bioassay. Furthermore, ATD did not react with rat prostatic or hypothalamic cytosol androgen receptors. 1,4,6-Androstatriene-17-ol-3-one, a possible metabolite of ATD in vivo, did react with prostatic and hypothalamic androgen receptors, but possessed no antiandrogenic activity in either bioassay. Thus, treatment of adult males with an aromatase inhibitor that inhibits both peripheral and central aromatization, and which has no apparent antiandrogenic activity, results in stimulation of LH and testosterone secretion. These data demonstrate that aromatization of androgens to estrogens plays an important role in negative feedback regulation of LH secretion and maintenance of normal testosterone levels in adult male primates.

Androstatrienes↗

Morphology of the oviducts and endometria of cynomolgus macaques during the menstrual cycle.

We sampled the reproductive tracts of 27 cynomolgus macaques during the menstrual cycle and correlated the cytologic changes in the oviductal epithelium with changes in the serum levels of estradiol (E2) and progesterone (P) and with the histology of the ovaries and the endometria. We identified an orderly sequence of changes in the oviductal epithelium from the early follicular to the late luteal phase, and we classified this sequence into eight stages, named as follows: preciliogenic, ciliogenic, ciliogenic-ciliated, ciliated-ciliogenic, ciliated-secretory, early regression, late regression and full regression. The preciliogenic and ciliogenic phases were coincident with menses and the early follicular phase. The ciliogenic-ciliated, ciliated-ciliogenic and ciliated-secretory phases during which the oviductal epithelium became progressively more differentiated were coincident, respectively, with the midfollicular, late follicular and periovulatory phases of the cycle. The early, late and full regression stages during which the epithelium became progressively more atrophied, deciliated and nonsecretory were coincident, respectively, with the early, mid and late luteal phases of the cycle. The cyclic changes in the endometrium of cynomolgus macaques were similar to those reported for the rhesus macaque.

Animals↗

Structural characteristics of the corpus luteum during implantation in the rhesus monkey (Macaca mulatta).

Corpora lutea were obtained from ten pregnant rhesus monkeys during implantation, and the ultrastructure of granulosa and theca lutein cells was characterized. Specimens were individually staged with regard to the extent of implantation and the relationship to the rise in circulating progesterone and estrogen which is characteristic of early pregnancy. Structural changes characteristic of granulosa lutein cells occurring during implantation included: change in form of endoplasmic reticulum from predominantly agranular tubules to predominantly granular cisternae; reduction in size and number of lipid droplets; increase in area occupied by the Golgi and increase in length of the cisternae of the Golgi complex; development of numerous microvillus-lined intracellular spaces; increase in numbers of membrane-bound dense bodies including peroxisomelike bodies, multivesicular bodies within lobopodia, and other lysosomelike bodies; and alterations of mitochondrial cristae. These changes were suggestive of the production of a secretory protein, rapid utilization of existing steroid precursor reserves for the production of progesterone, and a reduction in capability for steroid precursor accumulation and processing by granulosa lutein cells. Structural changes characteristic of theca lutein cells occurring during implantation included an increase in size and number of lipid droplets, an increase in agranular endoplasmic reticulum, and an increase in area occupied by the Golgi complex. These changes were suggestive of an increased capability for steroid precursor accumulation and processing, perhaps for estrogen production, by the theca lutein cells.

Animals↗

Dopamine: effects on prolactin and luteinizing hormone secretion in ovariectomized rhesus macaques after transection of the pituitary stalk.

Luteinizing hormone (LH) and prolactin (PRL) levels were compared in the serum of ovariectomized rhesus macaques (Macaca mulatta) with pituitary-intact (PI) and surgically transected pituitary stalks (SS). After stalk sectioning, LH levels declined and PRL levels rose dramatically. Chronic infusion of intermittent pulses of gonadotropin-releasing hormone (GnRH; 1 microgram/min for 6 of every 60 min) into SS females reinitiated LH secretion within a few days despite increased PRL secretion. Continuous infusion of dopamine (10 micrograms/min/kg of body weight) for 9 days suppressed PRL levels in GnRH-infused SS females to near normal without alteration in basal serum LH levels or pulsatile LH release. A comparable dopamine regimen also failed to modify serum LH patterns in PI monkeys. Immediately after cessation of dopamine, serum PRL levels rose sharply in both PI and SS animals. Injection of estradiol benzoate (42 micrograms/kg of body weight) into SS monkeys receiving GnRH infusions resulted initially in LH suppression and then in LH release. However, the magnitude of LH release was less and the latency to its onset was longer in SS animals given estrogen than in PI controls with similar serum estrogen concentrations. It is unclear whether the atypical pattern of the estrogen-induced LH release in SS monkeys was due to hyperprolactinemia or other deficiencies in this GnRH-infused model. However, these data indicate that the response of gonadotropes to GnRH stimulation was not altered by a direct action of either PRL or dopamine on the pituitary gland. Conversely, dopamine directly suppressed the lactotrope, which became hypersecretory immediately upon dopamine withdrawal. We have concluded that estrogen-induced inhibition and subsequent augmentation of LH release represents a direct action at a pituitary locus, although effects at additional, nonpituitary loci are not precluded.

Animals↗

The effects of prenatal diethylstilbestrol exposure on the genitalia of pubertal Macaca mulatta. II. Male offspring.

In order evaluate the potential embryotoxic and fetotoxic effects of in utero diethylstilbestrol (DES) exposure on the developing offspring, 19 pregnant rhesus monkeys were administered 1 mg/day DES orally beginning on either day 19 (group I), 100 (group II) or 130 (group III) or gestation and termination on the day of natural birth or cesarean section. Five of ten male offspring are alive at 7 years of age. At 4 1/2 years of age, three of these five offspring exhibited one or more abnormalities of the external genitalia, including testicular hypoplasia, preputial adhesions and undescended testes. Semen analysis following rectal electroejaculation and testicular biopsies at 5 1/2 years of age confirmed two cases of testicular hypoplasia. Semen evaluation, testicular biopsies and analysis of serum testosterone levels at 6 1/2 years of age indicated normal testicular morphology and function in all DES-exposed males as compared with colony controls. Our study, therefore, suggests that DES may affect maturation of the reproductive tract as indicated by a delay in the normal breakdown of preputial adhesions in addition to gross and microscopic evidence of testicular hypoplasia during the postpubertal period between 4 1/2 and 5 1/2 years of age. Further observations on breeding performance and fertility are required to evaluate the long-term effects of DES in this species.

Animals↗

Amniocentesis and antenatal sex determination in the rhesus monkey (Macaca mulatta).

Antenatal sex was correctly identified in 87.5% of the rhesus monkeys studied by evaluation of sex chromatin bodies in the exfoliated cells present in amniotic fluid. Fluid samples were obtained by either amniocentesis, amnioscopy, or by cesarean section at 80--120 days of gestation. Amniotic fluid concentrations of progesterone, total estrogen, and testosterone were correlated with fetal sex. Concentrations of these hormones decreased over the time period examined. Amniocentesis is a simple procedure which provides for routine fetal sex determination.

Amniocentesis↗

Reproductive and hormonal patterns in the African green monkey (Cercopithecus aethiops).

The results of breeding Cercopithecus aethiops under time-mated laboratory conditions and analysis of total estrogen, progesterone, and LH concentrations in plasma during the menstrual cycle and plasma estrogen and progesterone concentrations during pregnancy indicate that this species is a suitable alternative for the rhesus monkey as a model for investigations of reproductive function in man.

Animals↗

Further studies on the effects of lesions in the rostral hypothalamus on gonadotropin secretion in the female rhesus monkey (Macaca mulatta).

Bilateral radiofrequency lesions were stereotaxically placed in the rostral hypothalamus of four adult female rhesus monkeys. These lesions resulted in extensive destruction of the ventromedial preoptic-anterior hypothalamic area (POA-AHA) and included the suprachiasmatic nucleus as well as, with the exception of one animal, the organum vasculosum of the lamina terminalis. In three of these four animals, gonadotropin surges similar to those observed before surgery were elicited in response to either a spontaneous increment in serum estrogen concentration or an estradiol benzoate injection. This stimulatory action of estradiol on LH and FSH release was not demonstratable in the remaining lesioned animal, but estradiol benzoate injections also failed to elicit a gonadotropin discharge in one of a series of five normal control animals. These findings fail to support the view that destruction of the ventromedial POA-AHA in this species compromises the ability of the hypothalamicohypophysial apparatus to respond to the positive feedback action of estradiol. The diurnal variation in serum cortisol concentration was not interrupted by placement of the lesions in the ventromedial POA-AHA.

Animals↗

The arcuate nucleus and the control of gonadotropin and prolactin secretion in the female rhesus monkey (Macaca mulatta).

Attempts were made to destroy selectively the arcuate nucleus with radiofrequency current in adult female rhesus monkeys as a first step in identifying the areas of the mediobasal hypothalamus (MBH) that are responsible for the neural control of gonadotropin secretion in this species. Extensive or complete destruction of the arcuate region was produced in three animals and in two of these the lesion was confined primarily to the arcuate region and the dorsal aspect of the posterior median eminence. These lesions resulted in the cessation of LH and FSH secretion and blocked the positive feedback action of estradiol on gonadotropin release but did not appear to influence grossly basal thyroid and adrenocortical function, or to abolish GH discharge in response to insulin hypoglycemia. Adenohypophysial infarcts were not observed and exogenous LHRH and TRH induced marked discharges of the appropriate anterior pituitary hormones. In two additional animals with large hypothalamic lesions, destruction of the arcuate region was incomplete. In this group only partial inhibition of gonadotropin secretion was observed. LH and FSH secretion did not appear to be influenced in one animal bearing a large MBH lesion that entirely spared the arcuate region. Although serum prolactin remained at pre-lesion control levels after placement of the two relatively discrete lesions confined to the arcuate region, unambiguous increases in the secretion of this hormone were observed when the area of destruction encompassed tissue anterior and/or dorsal to the arcuate region. These observations suggest that the arcuate region is the primary structure mediating the hypothalamic control of gonadotropin secretion in the rhesus monkey. They also suggest that, in this species, the regions of the MBH involved with the regulation of gonadotropin release and those which control prolactin secretion are anatomically distinct.

Animals↗

On the sites of the negative and positive feedback actions of estradiol in the control of gonadotropin secretion in the rhesus monkey.

Ovariectomized rhesus monkeys bearing hypothalamic lesions which had abolished endogenous LHRH production, as evidenced by a profound reduction in gonadotropin secretion, but in which LH and FSH secretion was reestablished by a chronic intermittent iv infusion of synthetic LHRH (1 microgram/min for 6 min every hour) were used to investigate the sites of the negative and positive feedback actions of estradiol in the control of gonadotropin secretion. The administration of estradiol to such animals, while continuing the LHRH replacement regimen, resulted in a decline in circulating LH and FSH levels, followed by an unambiguous discharge of these hormones. The time course of this biphasic pattern of gonadotropin secretion was remarkably similar to that observed in response to estradiol administration in otherwise intact ovariectomized animals. These results suggest that, in the rhesus monkey, estradiol can exert both its negative and positive feedback actions on gonadotropin secretion at the level of the pituitary gland.

Animals↗