Biomedical subjects

V Mericq

Publications and source records attributed to V Mericq.

At least 19 recordsLinked to original sources

PubMed2006

Comparison of clinical, ultrasonographic, and biochemical differences at the beginning of puberty in healthy girls born either small for gestational age or appropriate for gestational age: preliminary results.

CONTEXT: There are limited and controversial data concerning puberty characteristics in girls born small for gestational age (SGA). OBJECTIVE: The objective of the study was to document clinical, ultrasonographic, and biochemical characteristics at the beginning of puberty in matched healthy girls born either SGA or appropriate for gestational age (AGA) recruited from the community. PATIENTS: Inclusion criteria were breast Tanner stage II and a body mass index between the 10th and 95th percentiles. INTERVENTIONS: Recruited subjects underwent a complete physical exam, bone age, and ultrasound measurements of the internal genitalia. Hormonal assessment included fasting early morning dehydroepiandrosterone sulfate, androstenedione, SHBG, inhibin-B, FSH, LH, estradiol (E2), 17-hydroxyprogesterone (17OH Prog), and testosterone. Thereafter, a GnRH agonist test (leuprolide 500 microg, sc) was performed with FSH and LH at time 3 and 24 h for E2, 17OH Prog, and testosterone. RESULTS: Sixty-five girls (35 AGA, 30 SGA) with a mean age of 9.9 +/- 1.03 (7.8-12.5) yr, similar bone age/chronological age (1.02 +/- 0.8 in AGA and 1 +/- 0.76 in SGA), median height of 1.35 +/- 0.06 cm, and similar waist to hip ratio were included. No differences in the presence of pubic hair, axillary hair, apocrine odor, or ultrasound measurements were found. SGA girls had increased baseline E2 as well as stimulated E2 and 17OH Prog. CONCLUSIONS: In a preliminary sample of lean, healthy girls recruited from the community born either SGA or AGA, we observed slight hormonal differences at the beginning of puberty. Longitudinal follow-up of this cohort will allow us to understand whether these differences are maintained and have a clinical impact in their pubertal development.

17-alpha-Hydroxyprogesterone↗

PubMed2006

Prematurity and insulin sensitivity.

Premature infants of low and extremely low birth weight represent a challenge for neonatal intensive care units and paediatricians. These neonates may be at increased risk of insulin resistance and diabetes perinatally and during childhood. During the first week of postnatal life, infants born prematurely are at risk of abnormalities in glucose homeostasis. Additionally, there are major differences in their glucose/insulin homeostasis compared with infants born at term. Preterm infants are at risk of hypoglycaemia, due to decreases in deposits of glycogen and fat that occur during the third trimester, and also to transient hyperinsulinaemia. Hyperglycaemia may also be observed in preterm infants during the perinatal period. These infants are unable to suppress glucose production within a large range of glucose and insulin concentrations, insulin secretory response is inappropriate, insulin processing is immature and there is an increased ratio of the glucose transporters Glut-1/Glut-2 in fetal tissues, which limits sensitivity and hepatocyte reaction to increments in glucose/insulin concentration during hyperglycaemia. In addition, increased concentrations of tumour necrosis factor alpha present in intrauterine growth retardation (IUGR) and induce insulin resistance. It has been proposed that the reduced insulin sensitivity may result from adaptation to an adverse in utero environment during a critical period of development. We have investigated postnatal insulin resistance in 60 children born with very low birth weight and either small for gestational age or at an appropriate size for gestational age. This study showed that IUGR, rather than low birth weight itself, was associated with increased fasting insulin levels. As poor fetal growth may be associated with the development of obesity, type 2 diabetes and the metabolic syndrome in later life, it is important that we continue to increase our understanding of the effects of IUGR on postnatal growth and metabolism.

Child Development↗

PubMed2005

Longitudinal changes in insulin sensitivity and secretion from birth to age three years in small- and appropriate-for-gestational-age children.

AIMS/HYPOTHESIS: Insulin resistance and type 2 diabetes risk in human subjects who were small-for-gestational-age (SGA) at birth may be a consequence of rapid early postnatal weight gain. MATERIALS AND METHODS: We prospectively studied early changes in fasting insulin sensitivity and insulin secretion, assessed by a short intravenous glucose tolerance test that was conducted several times from birth to 3 years of age in 55 SGA (birthweight below fifth percentile) newborns and in 13 newborns with a birthweight appropriate for gestational age (AGA). RESULTS: Most SGA infants showed postnatal upward weight centile crossing and by 3 years were similar in size to AGA infants. SGA infants had lower pre-feed insulin levels at postnatal age 48 h than AGA infants (median 34.4 vs 59.7 pmol/l, p<0.05), but by the age of 3 years they had higher fasting insulin levels (median 38.9 vs 23.8 pmol/l, p<0.005), which were related to rate of weight gain between 0 and 3 years (r=0.47, p=0.0003). First-phase insulin secretion did not differ between SGA and AGA infants, but SGA infants had a lower glucose disposition index (beta cell compensation) (median 235 vs 501 min mmol(-1) l(-1), p=0.02), which persisted after allowing for postnatal weight gain (p=0.009). CONCLUSIONS/INTERPRETATION: SGA infants showed a marked transition from lower pre-feed insulin and increased insulin sensitivity at birth to insulin resistance over the first 3 years of life. This transition was related to rapid postnatal weight gain, which could indicate a propensity to central fat deposition. The additional observation of reduced compensatory beta cell secretion underlines the need for long-term surveillance of glucose homeostasis in all SGA subjects, whether or not they show postnatal catch-up growth.

Birth Weight↗

PubMed2001

Regulation of growth plate chondrogenesis by bone morphogenetic protein-2.

Bone morphogenetic proteins (BMPs) regulate embryonic skeletal development. We hypothesized that BMP-2, which is expressed in the growth plate, also regulates growth plate chondrogenesis and longitudinal bone growth. To test this hypothesis, fetal rat metatarsal bones were cultured for 3 days in the presence of recombinant human BMP-2. The addition of BMP-2 caused a concentration-dependent acceleration of metatarsal longitudinal growth. As the rate of longitudinal bone growth depends primarily on the rate of growth plate chondrogenesis, we studied each of its three major components. BMP-2 stimulated chondrocyte proliferation in the epiphyseal zone of the growth plate, as assessed by [(3)H]thymidine incorporation. BMP-2 also caused an increase in chondrocyte hypertrophy, as assessed by quantitative histology and enzyme histochemistry. A stimulatory effect on cartilage matrix synthesis, assessed by (35)SO(4) incorporation into glycosaminoglycans, was produced only by the highest concentration of BMP-2. These BMP-2-mediated stimulatory effects were reversed by recombinant human Noggin, a glycoprotein that blocks BMP-2 action. In the absence of exogenous BMP-2, Noggin inhibited metatarsal longitudinal growth, chondrocyte proliferation, and chondrocyte hypertrophy, which suggests that endogenous BMPs stimulate longitudinal bone growth and chondrogenesis. We conclude that BMP-2 accelerates longitudinal bone growth by stimulating growth plate chondrocyte proliferation and chondrocyte hypertrophy.

Animals↗

PubMed2001

[Clinical and molecular study of Chilean patients with McCune-Albright syndrome].

BACKGROUND: McCune-Albright Syndrome (MAS) is characterized by precocious puberty, "cafe au lait" skin lesions and polyostotic fibrous dysplasia. It is caused by 4 post-zygotic mutations of G alpha s protein with a mosaic distribution. AIM: To describe the clinical presentation and to investigate the presence of the Arg by his substitution (R201H) in 14 girls with MAS. PATIENTS AND METHODS: We performed a clinical analysis of the patients and specific allele PCR in DNA obtained from leukocytes. RESULTS: Twelve of 14 patients presented with precocious puberty, one with cyclical vaginal bleeding and one with pathological bone fractures. Eight girls had polyostotic fibrous dysplasia, one had hyperthyroidism, four had pathological fractures, ten had ovarian cysts, six had breast hyperpigmentation and ten had "cafe au lait" skin lesions. We detected the R2O1H mutation in 10 of 14 patients. We found no difference in the severity of symptoms or in the age of presentation between the patients with and without the mutation. CONCLUSIONS: The R201H mutation can be detected in white blood cells, in approximately 70% of cases. Patients exhibit wide clinical variability with the same molecular defect. This suggests that tissues have different proportions of mutant cells.

Adolescent↗

PubMed2000

Regulation of fetal rat bone growth by C-type natriuretic peptide and cGMP.

C-type natriuretic peptide (CNP) and its high affinity receptor-B are expressed in fetal bones. Here we show that CNP accelerates longitudinal growth of fetal rat metatarsal bones in organ culture by several mechanisms. First, CNP stimulates chondrocyte proliferation in the proliferative zone as assessed by [3H]thymidine incorporation. Second, CNP stimulates cell hypertrophy as assessed by quantitative histology. Third, CNP stimulates cartilage matrix production as assessed by incorporation of 35SO4 into glycosaminoglycans. Natriuretic peptide receptor-B contains an intracellular guanylyl cyclase catalytic domain. We therefore hypothesized that cyclic GMP (cGMP) would reproduce the effects of CNP on fetal bones. Consistent with this hypothesis, we found that 8-Br-cGMP, like CNP, stimulates longitudinal growth and glycosaminoglycan synthesis. However, unlike CNP, cGMP inhibits proliferation of growth plate chondrocytes and has no effect on hypertrophy. We conclude that CNP stimulates longitudinal bone growth by increasing chondrocyte proliferation, chondrocyte hypertrophy, and cartilage matrix production. cGMP, a second messenger for CNP, reproduces some but not all of the effects of CNP, suggesting that other signal transduction mechanisms may also be involved.

Animals↗

PubMed2000

Retinoic acid is a potent regulator of growth plate chondrogenesis.

Vitamin A deficiency and excess both cause abnormalities in mammalian longitudinal bone growth. Because all-trans retinoic acid (RA) is synthesized from vitamin A, we hypothesized that RA regulates growth plate chondrogenesis. Consistent with this hypothesis, a single oral dose of RA reduced the height of the rat proximal tibial growth plate. To determine whether RA acts directly on growth plate, fetal rat metatarsal bones were cultured in the presence of RA. In this system, RA inhibited longitudinal bone growth by three mechanisms: 1) decreased chondrocyte proliferation, (assessed by 3H-thymidine incorporation), particularly in the proliferative zone of the growth plate; 2) decreased matrix synthesis (assessed by 35SO4 incorporation into glycosaminoglycans); and 3) decreased cell hypertrophy (determined histologically). The growth-inhibiting effects of RA were completely reversed by a retinoic acid receptor (RAR) antagonist. In the absence of exogenous RA, this antagonist accelerated bone growth, as did an RA-specific neutralizing antibody, suggesting that endogenous RA negatively regulates growth plate chondrogenesis. We conclude that RA, acting through RARs, negatively regulates longitudinal bone growth by inhibiting growth plate chondrocyte proliferation, chondrocyte hypertrophy, and matrix synthesis.

Alkaline Phosphatase↗

PubMed1999

Estrogen levels in girls with premature thelarche compared with normal prepubertal girls as determined by an ultrasensitive recombinant cell bioassay.

OBJECTIVE: Estradiol levels in girls with premature thelarche have not previously been well defined because of the lack of adequate sensitivity of previously available estradiol assays. The ultrasensitive recombinant cell bioassay for estradiol has made the study of estradiol levels in premature thelarche possible. We hypothesized that girls with premature thelarche have higher estradiol levels than normal prepubertal girls. STUDY DESIGN: We used an ultrasensitive recombinant cell bioassay to study estradiol levels in 20 girls with premature thelarche and 15 normal prepubertal girls less than 3 years of age. The 2 groups were compared by Student t test. RESULTS: Estradiol levels were significantly greater in the girls with premature thelarche (8.4 4. 5 pmol/L estradiol equivalents) than in the normal prepubertal girls (3.3 3.5 pmol/L estradiol equivalents; P <.01). The estradiol level was not significantly correlated with age, height, weight, body mass index, age at onset of thelarche, or the presence or absence of ovarian cysts. CONCLUSION: Girls with premature thelarche have significantly higher estradiol levels than normal prepubertal girls. This is consistent with the hypothesis that the mechanism of premature thelarche involves increased estradiol levels rather than increased sensitivity of breast tissue to normal estradiol levels.

Biological Assay↗

PubMed1998

Effects of eight months treatment with graded doses of a growth hormone (GH)-releasing peptide in GH-deficient children.

Stimulation of pituitary GH secretion with administered GHRH can be effective therapy for those GH deficient (GHD) patients whose disorder results from insufficient endogenous GHRH secretion. We have previously shown that most such patients also respond acutely to the GH-releasing peptides (GHRP's), which have a different mechanism of action from GHRH, with release of GH. In this study we tested whether the GH response to a newer GHRP, GHRP-2, would be sustained over time. Six prepubertal children with GHD and growth failure received stepwise increasing s.c. doses of GHRP-2, at 0.3, 1.0, and 3.0 micrograms/kg/day, in successive 2-month treatment periods, with monitoring of overnight 12 h episodic GH secretion and toxicity measures at the end of each period. During a fourth 2-month period, they received 3 micrograms/kg GHRP-2 together with 3 micrograms/kg s.c. GHRH. Serum levels of IGF-I and IGFBP-3 were also measured, and stadiometer height measurements were recorded. GHRP-2 administration produced a dosewise increase in overnight GH secretion. GH profiles showed that the effect of GHRP-2 injections was relatively brief, with little effect upon GH secretion later in the night. Serum levels of IGF-I and of IGFBP-3 did not increase. Growth velocity was higher during GHRP-2 treatment than during pretreatment and post-treatment evaluations. There were no side effects or toxicities observed. Thus GHRP-2 is well tolerated and is able to stimulate GH secretion. Formulations or routes of administration that allow for a longer duration of action will likely be needed to use GHRP-2 in therapy.

Adolescent↗

PubMed1997

Two different 5' splice site mutations in the growth hormone gene causing autosomal dominant growth hormone deficiency.

Four distinct types of isolated growth hormone deficiency (IGHD) have been described to date. Of these IGHD type II has been defined as having a dominant mode of inheritance. We performed a molecular genetic analysis of two patients clinically characterized as IGHD type II. One of the patients and her father shared a heterozygous G-A transition in the first 5' donor splice site of intron III. The second father and daughter studied also showed a heterozygous G-A transition in the fifth base from the 5' donor splice site in the same intron. Both mutations altered the correct splicing of the growth hormone pre-mRNA when the corresponding genes were expressed in COS-7 cells. We propose that both inherited mutations are responsible for IGHD type II in these patients.

Adult↗

PubMed1997

Optimizing growth hormone therapy during puberty.

During puberty, growth hormone (GH)-deficient children may experience difficulties achieving an appropriate pubertal growth spurt. We review the complex hormonal interactions which occur during puberty. At least two therapeutic strategies have been developed to optimize GH therapy during puberty. In the first strategy, the GH dose administered per kilogram of body weight is increased during puberty, in an attempt to mimic the physiological increase of GH which occurs during puberty. In the second strategy, luteinizing hormone-releasing hormone (LHRH) analogs are administered concomitantly with GH with the aim of delaying epiphyseal fusion. The efficacy of these strategies to increase final height has not previously been clearly demonstrated.

Adolescent↗

PubMed1997

Effects of luteinizing hormone-releasing hormone analog-induced pubertal delay in growth hormone (GH)-deficient children treated with GH: preliminary results.

To study the effect of delaying epiphyseal fusion on the growth of GH-deficient children, we studied 14 pubertal, treatment naive, GH-deficient patients (6 girls and 8 boys) in a prospective, randomized, placebo-controlled trial. Chronological age was 14.5 +/- 0.5 yr, and bone age was 11.6 +/- 0.3 yr (mean +/- SEM) at the beginning of the study. Patients were assigned randomly to receive GH and LH-releasing hormone (LHRH) analog (n = 8) or GH and placebo (n = 6) during 3 yr, with planned continuation of GH treatment until epiphyseal fusion. Patients were measured with a stadiometer and had serum LHRH tests, serum testosterone (boys), serum estradiol (girls), and bone age performed every 6 months. Patients treated with GH and LHRH analog showed a clear suppression of their pituitary-gonadal axis and a marked delay in bone age progression. We observed a greater gain in height prediction in these patients than in the patients treated with GH and placebo after 3 yr of treatment (mean +/- SEM, 14.0 +/- 1.6 vs. 8.0 +/- 2.4 cm; P < 0.05). These preliminary findings suggest that delaying epiphyseal fusion with LHRH analog in pubertal GH-deficient children treated with GH increases height prediction and may increase final height compared to treatment with GH alone.

Adolescent↗

PubMed1995

The effects of beta 1-adrenergic blockade on the growth response to growth hormone (GH)-releasing hormone therapy in GH-deficient children.

Acute suppression of SRIH secretion with a beta-adrenergic antagonist can increase the GH response to GHRH. To determine whether chronic beta-blockade could enhance the growth-promoting effects of GHRH therapy, we conducted a double blind, placebo-controlled, randomized, cross-over trial of coadministration of the selective beta 1-antagonist atenolol together with GHRH in 11 GH-deficient children. In randomly chosen order, each patient received two 12-month treatment periods with a single daily injection of GHRH (20 micrograms/kg, sc, at bedtime), plus daily oral administration of either atenolol (1 mg/kg) or placebo. The growth velocity increased, rising from a mean +/- SD of 2.6 +/- 0.4 cm/yr before treatment to 5.4 +/- 1.0 cm/yr during the first year of treatment with GHRH plus placebo and to 6.8 +/- 1.2 cm/yr during the first year of treatment with GHRH plus atenolol. The mean growth velocity during treatment with GHRH plus atenolol was significantly greater than that observed during GHRH plus placebo (P < 0.05). After cross-over, however, during the second year of therapy, we did not observe any significant differences in growth velocity between the two groups (4.2 +/- 1.4 vs. 3.9 +/- 0.8 cm/yr during treatment with GHRH plus placebo and GHRH plus atenolol, respectively). The mean 24-h serum GH levels were 1.4 +/- 0.9 micrograms/L during the baseline period, 1.3 +/- 0.2 and 2.0 +/- 1.4 micrograms/L during the first year of GHRH plus placebo and GHRH plus atenolol, respectively (P = NS), and 2.7 +/- 1.4 and 1.4 +/- 0.4 micrograms/L during the second year of GHRH plus placebo and GHRH plus atenolol, respectively (P < 0.05). This is the first demonstration that alteration of neurotransmitter action can enhance the therapeutic response to a hypothalamic releasing factor.

Adrenergic beta-1 Receptor Antagonists↗

PubMed1995

Growth hormone (GH) responses to GH-releasing peptide and to GH-releasing hormone in GH-deficient children.

The GH-releasing peptides (GHRPs) are a family of hexa- and heptapeptides that specifically stimulate GH secretion in normal adults and children. They would be an attractive potential form of therapy for GH deficiency (GHD) if they are also active in these patients. Their action, however, appears to result at least in part through hypothalamic responses, which may be impaired in GHD, and their ability to evoke a GH response in these patients must therefore be directly examined. We studied GH responses to the heptapeptide GHRP-1 in 22 prepubertal children with previously documented GHD and growth failure and compared them to responses to GHRH and the two peptides administered together. Patients received 1 microgram/kg GHRH-(1-44)NH2, 1 microgram/kg GHRP-1, or both, in random order. Tests were separated by at least 1 week. GHRP-1 evoked a significant GH response in 60% of the patients, comparable to the 68% who responded to GHRH. The magnitudes of the peak responses were similar (7.5 +/- 8.0 micrograms/L to GHRP-1 and 11.2 +/- 12.1 to GHRH), although the duration of the GH rise was briefer after GHRP-1. Both responses were lower than those previously observed in normal subjects. There was a marked synergy in responses when the two were given together; the GH peak (34.2 +/- 44.8 micrograms/L) significantly exceeded the sum of the individual responses, and the proportion of patients who responded (86%) was also higher. Thus, despite the absence of endogenous GHRH reflexes in most patients with GHD, these children can respond to GHRP-1 similarly to GHRH, and GHRP-1 can markedly enhance the response to GHRH. These results suggest that GHRPs or their analogs could form the basis for therapy of GHD.

Adolescent↗

PubMed1986

Effects of ketoconazole on rat ovarian steroidogenic enzymatic activities.

Ketoconazole (K) is an antifungal imidazole derivative which is a potent inhibitor of steroid biosynthesis in rodents and humans. To study the effect of K on rat ovarian steroidogenesis we measured the activities of five ovarian microsomal steroidogenic enzymes in K-treated rats and controls. Thirty hypophysectomized, gonadotropin-treated female adult rats were given either 2 mg K or water every 12 hours by mouth during 5 days. Mean ovarian weight was similar in both groups of animals. The K-treated group had an estradiol (E) serum concentration of 176 +/- 48 pg/ml whereas it was 278 +/- 56 pg/ml in the control group (NS). The K-treated animals had decreased activities of the 17,20-desmolase, 17-ketosteroid-reductase and aromatase enzymes. The 3 beta hydroxysteroid-dehydrogenase and 17-hydroxylase activities were similar in both groups. We conclude that K directly inhibits the activities of the 17,20-desmolase, 17-ketosteroid-reductase and aromatase enzymes in the rat ovary.

17-Hydroxysteroid Dehydrogenases↗

PubMed1985

The effects of prolactin on rat testicular steroidogenic enzyme activities.

To investigate whether hyperprolactinemia directly affects rat testicular steroidogenesis, we examined the effects of prolactin (PRL) on microsomal 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) 17-hydroxylase (17-OH), 17,20-desmolase (17,20-D), 17-ketosteroid reductase (17-KSR) and aromatase enzyme activities. Adult hypophysectomized, gonadotropin-treated Fisher rats were rendered hyperprolactinemic by isografting pituitaries under the kidney capsule. The controls received skeletal muscle. All rats were sacrificed 7 days later and serum PRL was measured in each animal. PRL levels were 198 +/- 14 ng/ml in the hyperprolactinemic rats and 4.3 +/- 0.6 ng/ml in the controls (P less than 0.001). The testes were resected, pooled according to PRL levels, and microsomes were prepared from each pool. The activities of the 3 beta-HSD, 17-OH, 17,20-D, 17-KSR and aromatase were measured using as substrates 14C dehydroepiandrosterone, progesterone, 17-hydroxyprogesterone, androstenedione and testosterone, respectively. Hyperprolactinemia was associated with significant decreases in 3 beta-HSD, 17-OH, 17,20-D, 17-KSR and aromatase activities when compared to controls (P less than 0.005). We conclude that prolactin may have a direct effect on rat testicular steroidogenesis which appears to be independent of changes in gonadotropin secretion.

Animals↗

PubMed1985

Direct effect of the luteinizing hormone releasing hormone analog D-Trp6-Pro9-Net-LHRH on rat ovarian steroidogenesis.

The luteinizing hormone releasing hormone analog D-Trp6-Pro9-Net-LHRH (LHRHa) inhibits rat ovarian estradiol secretion. To determine whether LHRHa decreases serum estradiol concentrations solely by inhibiting gonadotropin secretion or, in addition, by influencing directly ovarian estradiol biosynthesis, we examined the effects of LHRHa on the activities of 5 key ovarian steroidogenic enzymes. Fifty hypophysectomized, gonadotropin-treated rats were given either LHRHa (1 microgram/day) or saline sc during 7 days. The LHRHa treated animals exhibited a significant decrease in serum estradiol when compared with the control group (461 +/- 30 vs 31 +/- 5 pg/ml, mean +/- SE, P less than 0.001). The changes in estradiol concentration were associated with decreases in ovarian weight (372 +/- 19 vs 185 +/- 11 mg, P less than 0.001) and in the microsomal enzyme activities of 3 beta-hydroxysteroid dehydrogenase (156 +/- 5 vs 53 +/- 4 nmol/mg prot/min, P less than 0.001), 17 hydroxylase (4.7 +/- 0.8 vs 3.7 +/- 0.7 nmol/mg prot/min, P less than 0.002), 17,20 desmolase (279 +/- 14 vs 50 +/- 7 pmol/mg prot/min, P less than 0.001), 17 keto-steroid reductase (132 +/- 11 vs 6 +/- 1 nmol/mg prot/min, P less than 0.001), and aromatase (19 +/- 1.5 vs 0.9 +/- 0.1 nmol/mg prot/min, P less than 0.001) in LHRHa treated animals. These findings indicate that LHRHa can inhibit directly rat ovarian estradiol biosynthesis.

17-Hydroxysteroid Dehydrogenases↗

PubMed1984

The effects of prolactin on rat ovarian function.

Hyperprolactinemia has been associated with several reproductive disorders. To investigate whether hyperprolactinemia directly affects rat ovarian function, we examined the ovarian histopathology and the activities of the four ovarian enzymes 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), 17-hydroxylase (17-OH), 17,20-desmolase (17,20-D) and aromatase in hyperprolactinemic rats and controls. Hypophysectomized, gonadotropin-treated Fisher rats were made hyperprolactinemic by isografting pituitary glands under the kidney capsule. The control animals received skeletal muscle. The ovaries were resected, pooled according to prolactin levels and microsomal enzyme activities were measured from each pool. Prolactin (PRL) levels were 344 +/- 23 ng/ml in the hyperprolactinemic rats and 18 +/- 5 ng/ml in the controls (p less than 0.001). Estradiol concentrations were 609 +/- 47 pg/ml in the hyperprolactinemic animals and 56 +/- 13 pg/ml in the controls (p less than 0.001). Ovarian and uterine weights were significantly higher in the hyperprolactinemic rats (p less than 0.02). Ovarian histopathology demonstrated benign polycystic transformation in the hyperprolactinemic animals. Hyperprolactinemia had no effect on 3 beta-HSD, but was associated with significant decreases in the 17-OH, 17,20-D and aromatase activities when compared to controls (p less than 0.001). We conclude that prolactin has a direct effect on rat ovarian function which appears to be independent of changes in gonadotropin secretion.

3-Hydroxysteroid Dehydrogenases↗