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Two experiments were conducted to determine whether mifepristone (RU486) and PGF

An experiment was conducted to determine the effect of prostaglandin F2alpha (PGF2alpha) on luteal synthesis of progesterone (P4) and related progestins. Sixteen beef heifers were assigned in equal numbers to four groups in a 2x2 factorial arrangement of treatments. The experiment consisted of two levels of PGF2alpha analog (0 and 500 microg) and two levels of time (4 and 24 h after injection) of corpus luteum collection. All heifers were injected intravenously with saline (2 ml) or PGF2alpha (cloprostenol) on day 8 of the estrous cycle (estrus=day 0). Jugular blood was collected at 0, 1, 2, 3, 4 and 20, 21, 22, 23, and 24 h after injection. Resulting sera were analyzed for P4 by use of radioimmunoassay. Luteal tissue was analyzed by gas chromatography/mass spectrometry for P4, 20beta-hydroxyprogesterone, pregnenolone, and allopregnanolone (3beta-hydroxy-5alpha-pregnan-20-one). Treatment with PGF2alpha reduced serum concentrations of P4 as early as 1 h after injection (P0.005) and steroid levels remained low over 24 h. Similarly, administration of PGF2alpha caused a decline in luteal P4 (P0.005), 20beta-hydroxyprogesterone (P0.10), and pregnenolone (P0.05). In contrast, treatment with PGF(2alpha) caused an increase in luteal allopregnanolone over time (time x treatment interaction; P0.05). These data are interpreted to suggest that PGF2alpha promotes conversion of P4 to the metabolite allopregnanolone. more...

The male-oriented ram is a unique and valuable animal model for the study of hormonal, developmental and genetic contributions to sexual partner preference. Unlike most other mammalian models that are in use currently, variations in sexual attraction occur spontaneously in domestic ram populations. It is estimated that as many as 8-10% of rams exhibit a sexual partner preference for other males, classifying them as male-oriented rams. Studies have failed to identify any compelling social factors that can predict or explain the variations in sexual partner preferences of rams. Nor is there consensus on the endocrine and sensory responsiveness of male-oriented rams to other rams. However, a number of studies have reported differences in brain structure and function between male-oriented and female-oriented rams, suggesting that sexual partner preferences are neurologically hard-wired. Recently, we identified a sexually dimorphic nucleus (oSDN) in the sheep preoptic area-anterior hypothalamus. The oSDN is larger in female-oriented rams than in male-oriented rams and similar in size in male-oriented rams and ewes. In addition, mRNA levels for aromatase in the oSDN were higher in males than in females and were higher in female-oriented rams than in male-oriented rams. These results suggest a relationship between steroid hormones, specifically estrogens and oSDN morphology. In this review, we provide an overview of sexual behavior in rams and discuss the multiple factors that may contribute to the development and adult expression of same-sex partner preferences in rams. more...

The bovine corpus luteum contains a myristoylated alanine-rich C kinase substrate (MARCKS) protein known to crosslink actin filaments in the cytoskeletal cortex associated with the plasma membrane. We conducted experiments to determine whether concentrations of MARCKS mRNA and protein in the bovine corpus luteum varied during the estrous cycle. Using Northern blots probed with a MARCKS cDNA, we found that luteal concentrations of MARCKS mRNA were greatest on d 4, 8, and 12 and markedly reduced on d 16 of the cycle (p0.08). Similarly, Western blot analysis of luteal proteins revealed that concentrations of MARCKS protein were greatest on d 8 and least on d 16 of the cycle (p0.01). Exposure of slices from a d 8 corpus luteum to prostaglandin F2alpha (PGF2alpha) during a 10-min incubation in the presence of [32P]-ortho-phosphate resulted in enhanced phosphorylation of MARCKS in membrane and cytosolic fractions compared to that of controls. We therefore concluded that expression of the luteal MARCKS protein gene may be regulated and that PGF2alpha-induced phosphorylation of this protein is attributable to activation of protein kinase C. more...

A study was conducted to investigate the effects of exogenous melatonin on serum concentrations of estradiol-17 beta (E2) and progesterone (P4) and uterine prolactin (PRL) receptor concentrations in mated mink. In Experiment 1, two groups of adult, standard dark, female mink were mated to fertile males on March 8 or 9. On March 16, mink in group 1 (N = 8) received an empty Silastic implant inserted sc in the interscapular region and served as controls. Mink in group 2 (N = 8) received an implant containing 10 mg crystalline melatonin. On April 2, all animals were lightly anesthetized and blood samples collected via cardiac puncture were analyzed for serum concentrations of E2 and P4. Animals were subsequently sacrificed and uterine samples collected for analysis of PRL receptor concentrations. In Experiment 2, adult female mink were assigned randomly to three treatment groups and mated to fertile males between March 6 and 9. On March 16, mink in group 1 (N = 6) received empty Silastic implants and served as controls. Mink in group 2 (N = 6) received a Silastic implant containing 10 mg melatonin. Animals in group 3 (N = 6) received an implant containing 10 mg melatonin and in addition each mink was given daily sc injections of P4 (1 mg) from March 21 to April 5. At this time the mink were sacrificed, the number of implantation sites recorded, and uteri collected for quantification of PRL receptors. In Experiment 1, exogenous melatonin reduced serum P4 concentrations to almost nondetectable levels (controls, 8.08 +/- 0.73 vs treated, 0.82 +/- 0. 12 ng/ml; P0.001) and resulted in increased concentrations of E2 (controls, 13.3 +/- 1.9 vs treated, 22.0 +/- 1.9 pg/ml; P0.01). Uterine PRL receptor concentrations decreased (P0.05) from 37.74 +/- 9.37 fmol/mg protein (controls) to 23.74 +/- 9.03 fmol/mg protein in response to melatonin treatment. In those mink treated with melatonin plus P4 (Experiment 2), uterine PRL receptor concentrations were increased to levels not significantly different than those of controls. None of the mink treated with melatonin alone or in combination with P4 exhibited implantation. Uteri of mink treated with melatonin or melatonin plus P4 did not differ in weight but tended to weigh less than uteri of control mink. These data suggest that a high systemic ratio of P4 to E2 is essential for production of the uterine PRL receptor in mink and supports the findings of others that implantation in mink cannot be initiated with P4 alone. more...

Experiments were conducted to determine the in vivo and in vitro effects of metabolites of eicosapentaenoic acid on ovine luteal function. Injection of 750 micrograms methyl eicosapentaenoic acid (EPA) or methyl 12(R),13(S)-dihydroxyeicosapentaenoic acid (12,13-diHEPE) into the ovarian artery of ewes on day 10 of the estrous cycle caused a reduction in serum concentrations of progesterone by 48 h posttreatment compared with levels of this steroid in arachidic acid-treated controls (p0.005). Although mean serum concentrations of progesterone in methyl EPA-treated ewes during the remainder of the cycle did not differ from those in control ewes, levels in methyl 12,13-diHEPE-treated ewes remained significantly suppressed. Duration of the estrous cycle did not differ among treatment groups (p0.05), but more of the methyl 12,13-diHEPE-treated animals (3/5) had exhibited estrus within 3 days after injection than methyl EPA-treated (1/5) or control ewes (0/5). Slices of corpus luteum removed from ewes on day 10 of the estrous cycle were incubated with arachidic acid (controls), 12,13-diHEPE or docosatetraenoic acid (DTA). Regardless of fatty acid treatment, all tissues retained the ability to produce basal levels of progesterone during subsequent incubation. Luteal slices previously exposed to arachidic acid or DTA exhibited an increase in progesterone production in response to subsequent treatment with LH (p0.05). In contrast, luteal slices incubated with 12,13-diHEPE did not respond to LH with a significant increase in production of this steroid above that observed in controls. All tissues displayed a marked increase in progesterone synthesis upon treatment with 8-Br-cAMP relative to incubation of tissue alone (p0.001). Subcellular distribution of [14C]-12,13-diHEPE in luteal cells after incubation revealed that the majority of the fatty acid was associated with the plasma membrane. These data suggest that metabolites of eicosapentaenoic acid with hydroxyl groups on adjacent carbon atoms interfere with luteal function in the ewe, perhaps in part by altering luteal response to LH. more...

Experiments were conducted to examine the effect of a cyclopropenoid fatty acid (CPFA) on progesterone (P4) production by the ovine corpus luteum (CL) during the estrous cycle. Ewes in Exp 1 and 2 were laparotomized on day 2 of the estrous cycle, and animals with CL in both ovaries were subjected to unilateral ovariectomy. Ewes with CL in one ovary only were not ovariectomized. During surgery, ewes were injected with a mixture of fatty acids (sterculic acid, 39%; palmitic, 29%; linoleic, 12%; malvalic acid, 9%; oleic, 8%; stearic, 3%) containing 500 micrograms sterculic acid (SA; Exp 1), 750 micrograms SA, or 750 micrograms oleic acid (Exp 2) via the artery supplying the ovary bearing the CL. Control ewes were similarly injected with vehicle only (0.1-0.2 ml dimethylsulfoxide; Exp 1 and 2, respectively). Sera from blood samples collected at 15-min intervals for 1 h after injection or once daily on alternate days of the cycle after surgery were analyzed for LH and P4, respectively. In Exp 3, slices of CL removed from five ewes on day 10 of the cycle were incubated for 90 min in medium containing 100 ng/ml SA or vehicle (10 microliters dimethylsulfoxide). Slices were then reincubated for 90 min in medium containing 10 ng/ml oLH or saline (10 microliters). Tissue and medium were analyzed for P4. Injection of 500 micrograms SA suppressed serum levels of P4 (P less than 0.01), but did not alter mean cycle length. Injection of 750 micrograms SA reduced serum concentrations of P4 and shortened estrous cycle duration (P less than 0.005). Oleic acid (750 micrograms) or as much as 1.9 mg of a mixture of fatty acids devoid of CPFA had no effect on cycle length or serum levels of P4, suggesting that altered luteal function was due to the type and not the quantity of fatty acid injected. Treatments had no effect on serum concentrations of LH. Preincubation with SA interfered with the ability of luteal slices to synthesize P4 when subsequently incubated alone or with ovine LH (P less than 0.01). It is concluded that SA acts on the CL to impair steroidogenesis and ultimately cause luteal regression. more...

This study tested the hypothesis that aromatization of testosterone to estradiol is necessary for sexual differentiation of the sheep brain. Pregnant ewes (n = 10) were treated with the aromatase inhibitor 1,4,6- androstatriene-3,17-dione (ATD) during the period of gestation when the sheep brain is maximally sensitive to the behavior-modifying effects of exogenous testosterone (embryonic d 50-80; 147 d is term). Control (n = 10) ewes received vehicle injections. Fifteen control lambs (7 males and 8 females) and 17 ATD-exposed lambs (7 males and 10 females) were evaluated for sexually dimorphic behavioral and neuroendocrine traits as adults. Prenatal ATD exposure had no significant effect on serum concentrations of androgen at birth, growth rates, expression of juvenile play behaviors, or the onset of puberty in male and female lambs. Rams exposed to ATD prenatally exhibited a modest, but significant, decrease in mounting behavior at 18 mo of age. However, prenatal ATD exposure did not interfere with defeminization of adult sexual partner preferences, receptive behavior, or the LH surge mechanism. In summary, our results indicate that aromatization is necessary for complete behavioral masculinization in sheep. However, before we can conclude that aromatization does not play a role in defeminization of the sheep brain, it will be necessary to evaluate whether intrauterine exposure of male fetuses to higher doses of ATD for a more extended period of time can disrupt normal neuroendocrine and behavioral development. more...

Experiments were conducted to characterize the nongenomic effects of progesterone (P4) on binding of oxytocin (OT) to its receptor and signal transduction in the ovine endometrium. The dose-response relationship of P4 to OT binding was examined. Membranes from endometrial tissue of ovariectomized hormone-treated ewes were preincubated in the presence of P4 for 1 h followed by OT receptor analysis. P4 interfered with the binding of OT in a dose-dependent manner. Endometrium was then recovered from cyclic ewes and divided into explants. Treatment consisted of two dosages of P4 and two dosages of OT. Explants were analyzed for total inositol monophosphate, bisphosphate (IP(2)), and trisphosphate (IP(3)) content. Preincubation with P4 for 10 min significantly interfered with OT stimulation of IP(2) and IP(3) synthesis. Oxytocin increased monophosphate production, but there was no detectable effect of P4. In the next experiment, endometrial explants were cultured in the absence or the presence of arachidonic acid. Explants were then exposed for 1 h to medium containing vehicle or P4. After incubation, explants were challenged with OT and the media were collected and analyzed for 13,14 dihydro-15-keto prostaglandin F(2alpha) by RIA. Treatment of explants with AA increased PGF(2alpha) content compared with that of controls. Brief exposure to P4 significantly decreased OT-induced PGF(2alpha) secretion from explants previously exposed to medium or AA. Collectively, these data are interpreted to indicate that the observed reduction in OT-induced IP(2) and IP(3) production and OT-induced PGF(2alpha) secretion was due to P4 inhibition of OT binding to its receptor. more...

Progesterone (P4) has been reported to inhibit oxytocin (OT) binding to its receptor in isolated murine endometrial membranes. The purpose of the present research was to 1). examine the in vivo and in vitro effect of P4 on the binding of OT to its receptor in the ovine endometrium and 2). determine whether the endometrial plasma membranes have high-affinity binding sites for P4. Ovariectomized ewes were pretreated with a sequence of estradiol-17beta (2 days) and P4 (5 days) before being treated with estradiol-17beta plus either vehicle (corn oil), P4, or P4 + mifepristone (RU 486) for 3 consecutive days. Treatment of ewes with 10 mg P4/day for 3 days suppressed binding of OT (P0.01) compared with that of controls, whereas concomitant treatment with the progestin antagonist RU 486 (10 mg/day) blocked the effect of P4. Similarly, incubation of endometrial plasma membranes with P4 (5 ng/ml) inhibited binding of OT (P0.05), whereas this effect of P4 was blocked by the presence of RU 486 (10 ng/ml). By radioreceptor assay, the endometrial plasma membranes were found to contain a high-affinity binding site for P4 and the progestin agonist promegestone (Kd 1.2 x 10-9 and 1.74 x 10-10M, respectively). Incubation of endometrial plasma membranes with P4 (5 ng/ml) significantly increased the concentration of progestin binding sites. Binding of labeled promegestone (R 5020) was competitively inhibited by excess unlabeled R 5020, P4, RU 486, and OT but not by estradiol-17beta, cortisol, testosterone, and arginine vasopressin. These data suggest a direct suppressive action of P4 on the binding of OT to OT receptors in the ovine endometrial plasma membrane. more...

The aim of the present study was to determine whether the fetal lamb brain has the capacity to aromatize androgens to estrogens during the critical period for sexual differentiation. We also determined whether administration of the aromatase-inhibitor 1,4,6-androstatriene-3,17-dione (ATD) could cross the placenta and inhibit aromatase activity (AA) in fetal brain. Eight pregnant ewes were utilized. On Day 50 of pregnancy, four ewes were given ATD-filled Silastic implants, and the other four ewes received sham surgeries. The fetuses were surgically delivered 2 wk later (Day 64 of gestation). High levels of AA (0.8-1.4 pmol/h/mg protein) were present in the hypothalamus and amygdala. Lower levels (0.02-0.1 pmol/h/mg protein) were measured in brain stem regions, cortex, and olfactory bulbs. The Michaelis-Menten dissociation constant (K(m)) for aromatase in the fetal sheep brain was 3-4 nM. No significant sex differences in AA were observed in brain. Treatment with ATD produced significant inhibition of AA in most brain areas but did not significantly alter serum profiles of the major sex steroids in maternal and fetal serum. Concentrations of testosterone in serum from the umbilical artery and vein were significantly greater in male than in female fetuses. No other sex differences in serum steroids were observed. These data demonstrate that high levels of AA are found in the fetal sheep hypothalamus and amygdala during the critical period for sexual differentiation. They also demonstrate that AA can be inhibited in the fetal lamb brain by treating the mother with ATD, without harming fetal development. more...

Research was conducted to determine whether seasonal changes in prolactin secretion occur in nonpregnant female African elephants and to examine potential functional interrelationships between secretion of prolactin, cortisol, and progesterone. Weekly blood samples were taken for 18 months from four female African elephants and the sera were analyzed by RIA for progesterone, cortisol, and prolactin concentrations. There was no significant effect of season on serum concentrations of prolactin. Estrous cycles averaged 14 weeks in length and were composed of a 9-week luteal phase and a 5-week follicular phase (based on progesterone concentrations consistently200 and200 pg/ml, respectively). Estrous cycle synchronicity was evident between pairs of elephants. Serum concentrations of prolactin (3.91 +/- 0.69 ng/ml; range: 0.84-15.8 ng/ml) were significantly lower during the luteal, compared with the follicular, phase (P0.0001; t test) and were positively correlated with serum concentrations of cortisol (r = 0.14; P0.05). Mean (+/-SE) serum concentration of cortisol was 5.7 +/- 1.3 ng/ml (range: 1.4-19.3 ng/ml), and concentrations of this adrenal steroid were negatively correlated with progesterone concentrations (r = -0.15; P0.01). Increased serum concentrations of prolactin detected during the follicular phase suggest that this hormone may be regulated by ovarian estrogens and may play a role in modulating ovarian function in the elephant. more...

Research was conducted to determine the nature of the isoforms of protein kinase C (PKC) present in the bovine (Bos taurus) corpus luteum (CL) and their subcellular distribution. Western blot analysis was performed using isozyme-specific polyclonal antibodies and revealed that the bovine corpus luteum contains the alpha and epsilon isozymes of PKC, but not the beta, gamma, delta or zeta isozymes. Subcellular fractionation demonstrated that the alpha and epsilon isozymes of PKC were present in both the cytosolic and plasma membrane fractions. Densitometric measurements of Western blots of the subcellular luteal PKC fractions indicated that PKC alpha was found predominantly in the cytosolic fraction, whereas the majority of PKC epsilon was associated with the plasma membrane. more...

Two experiments were conducted to evaluate the effects of bromocriptine, melatonin (MLT), and 17 beta-estradiol (E2) on uterine physiology in mink (Mustela vison). In Expt. 1, summer-anestrous mink were injected sc daily with 2 mg bromocriptine or vehicle (n = 20 each) for 14 days. On Day 14, both groups were divided into two subgroups and injected sc with either 100 micrograms E2 or vehicle. Mink were bled immediately prior to euthanasia (24 hr after E2) and the sera analyzed for prolactin (PRL), E2 and progesterone (P4). At necropsy, aliquots of uterine tissue (n = 5) were used to measure in vitro oxidation of [14C]glucose, incorporation of [3H]thymidine into DNA and [14C]leucine into protein, and nuclear concentrations of estrogen receptor (ER) and P4 receptor (PR). In Expt. 2, anestrous mink were assigned to one of two treatment groups or a control group (n = 5 each). In mid-summer, groups 1 and 2 were implanted with 10 mg Silastic MLT implants. Seventeen weeks later, mink in group 1 received 100 micrograms E2 (sc) while group 2 and nonimplanted controls (group 3) were injected with vehicle. Mink were sacrificed 24 hr after injection and levels of PRL, E2, P4, ER, and PR determined. Bromocriptine suppressed serum concentrations of PRL (P < 0.001), increased serum levels of E2 (P < 0.05) and levels of PR (P < 0.01), but had no effect on levels of P4, uterine weight, glucose oxidation, DNA and protein synthesis, or concentrations of ER.(ABSTRACT TRUNCATED AT 250 WORDS) more...

The first two papers in this issue of Biology of Reproduction are minireviews derived from talks delivered at the 36th Annual Meeting of the Society for the Study of Reproduction, July 19–July 22, 2003, in Cincinnati, Ohio. The minisymposium, titled Steroid Regulation of Uterine Function in Domestic Animals, was organized by Dr. Fredrick Stormshak and included presentations by Dr. Thomas E. Spencer, Dr. Alan K. Goff, and Dr. Michael J. Fields. The papers included here were submitted to the Editorial office of Biology of Reproduction and were subjected to the same standards of peer review as all manuscripts published in the journal. more...

Experiments were conducted to examine the effects of exogenous GnRH and LH on serum concentrations of progesterone (P4) in the ewe. Ewes in Exp. 1 and 2 were laparotomized on d 2 of an estrous cycle and ewes with corpora lutea (CL) in both ovaries were unilaterally ovariectomized. Ewes with CL in one ovary only were not ovariectomized. While they were anesthetized, ewes (n = 5) were injected with 25 micrograms GnRH (Exp. 1) or 50 ng GnRH (Exp. 2) into the artery supplying the ovary bearing the CL. Control ewes (n = 5 in each experiment) were injected similarly with saline. In Exp. 3, six ewes were injected i.v. (jugular) on d 2 with 100 micrograms oLH (t = 0) and 50 micrograms oLH at 15, 30 and 45 min; six control ewes were injected similarly with saline. Jugular blood was collected from all ewes at frequent intervals after treatment for LH analysis and on alternate days of the cycle through d 10 or 11 for P4 analysis. Treatment with 25 micrograms GnRH increased serum concentrations of LH at 15, 30, 45 and 60 min postinjection (P less than .001) and reduced serum concentrations of P4 on d 7 through 11 (treatment x day interaction; P less than .05). Injection with 50 ng GnRH caused a slight increase in serum concentrations of LH at 15 min but had no effect on serum concentrations of P4.(ABSTRACT TRUNCATED AT 250 WORDS) more...

The present study was conducted to determine if specific binding sites for prolactin (PRL) are present in the uterus of the mink. Uteri of anestrous mink were homogenized and subjected to differential centrifugation into three particulate fractions, 1500, 15 000 and 50 000 X g. Binding of [125I]oPRL to membranes in an aliquot (200-400 micrograms protein) of the 50 000 X g particulate fraction was quantified. Time and temperature for optimal binding were 18 h at 25 degrees C. Scatchard plot analysis revealed a single set of binding sites for PRL with a Kd of 8.25 X 10(-11) +/- 0.68 M. The maximum amount of [125I]oPRL bound was 28 fmoles/mg protein. Prolactin binding sites were detected in both the uterus and kidney of mink, but not in skeletal muscle, spleen, diaphragm or lung. These data indicate that uterine cell membranes of the mink contain sites that bind prolactin with high affinity. more...

The relationship of glucocorticoid secretion to artificial light-induced, early winter priming of pelage in ranch mink was investigated. On December 13, 1977, 16 mature female mink were exposed to natural light. On June 26, 1978, the animals were assigned randomly to one of two groups. Animals in Group 1 were housed in a light-control facility and subjected to 6 hr of artificial light daily and ambient temperatures until November 27, 1978. Animals in Group 2 served as controls and were exposed to natural light. Samples of blood and measurements of the fur and vulva were taken biweekly throughout the year. Concentrations of total glucocorticoids in serum were determined by competitive protein-binding assay. The pelage of mink reared under reduced artificial light was fully prime by October 31, while that of control animals did not become prime until November 27 (time x light regimen interaction, P less than .05). A seasonal effect (P less than .01) on total glucocorticoid concentrations in serum of control mink was revealed by a pattern of three peaks over the 12-month period. The pattern of glucocorticoid secretion was not affected by exposure of mink to reduced artificial light. Maximum concentrations of total glucocorticoids in serum occurred on the same date (September 5) in both groups, although levels were significantly higher in the light-treated mink (44.5 +/- 10.4 ng/ml) than in the controls 26.9 +/- 5.7 ng/ml). Fur growth was positively correlated with total glucocorticoid concentrations in serum during the period from June to December (overall r = .14, P less than .05). Both length and width of the vulva increased (P less than .01) during February and March in animals reared under natural light. These data suggest that the increased secretion of glucocorticoids induced by exposure of mink to reduced artificial light may be involved in promoting early priming of the winter pelage of these animals. more...

An experiment was conducted to determine the effects of a reduced daily photoperiod and exogenous melatonin on serum prolactin levels of mink during the autumn molt and growth of the winter pelage. During the last week of June, adult standard dark female mink (Mustela vision) were exposed to natural changes in daylength (controls), a reduced photoperiod of 6 h light: 18 h dark (6L:18D) or exposure to natural changes in daylength and treated with melatonin (10 mg) in a Silastic implant inserted subcutaneously over the scapular area. Beginning July 2, and continuing through October 22, blood samples were collected at nine biweekly intervals, and serum prolactin concentrations were quantified by a heterologous double antibody radioimmunoassay. Both reduced photoperiod and exogenous melatonin caused serum prolactin levels to decline rapidly after mid-July, resulting in concentrations that were significantly lower than those of controls 6 to 8 wk earlier. These data suggest that growth of the winter pelage of mink is strongly associated with declining prolactin levels. It appears that part of the photoperiodic-induced effects on fur growth of the mink are mediated through melatonin and its effects on prolactin synthesis and/or secretion. more...

A study was conducted to determine the effects of exogenous melatonin and bromocriptine (CB-154), an inhibitor of prolactin synthesis and secretion, on the induction of winter fur growth in mink. Melatonin (10 and 120 mg) was administered to mink (N = 5/group) via silastic implants inserted sc over the scapular area during the last week of June 1985. Treatment of mink (N = 5) with CB-154 alone or in combination with 10 mg melatonin (N = 5) consisted of daily sc injections of 2 mg of the drug in sterile saline from June 25 through July 30. Control animals (N = 5) did not receive injections of vehicle or sham implants. Administration of CB-154 alone or in combination with 10 mg melatonin, as well as 120 mg melatonin alone, initiated growth of the winter fur significantly earlier than that of controls or mink treated with 10 mg melatonin (P less than 0.05). These data suggest that inhibition of prolactin secretion by melatonin is requisite for induction of molt of summer fur and growth of winter fur of mink. more...