The effect of periovulatory imbalance of prolactin on the expression of prolactin receptors in rat ovary cells

Using the technique of immunohistochemistry in combination with cytophotometry, we have studied the effect of periovulatory hyper- and hypoprolactinemia on the expression of prolactin receptors in various cell types of rat ovaries during early estrus. It has been shown that intense specific staining of oocytes is positively controlled by prolactin. The maximal intensity of specific staining was found in cells of the cumulus and the inner layer of granulosa cells in mature follicles; staining intensity gradually diminished towards the outer boundary cell layer. Postovulatory follicles are distinct from those mature follicles in which there was no ovulation in their more intense manifestation of prolactin receptors in cells of the inner layer and cumulus, as well as in increased positive staining (after prolactin administration) only in the granulosa layer cells closest to theca. In follicles which did not ovulate by the time of the early estrus, prolactin administration leads to a proportional growth of specific immunoreactivity in all cell layers of the granulosa. The administration of bromocryptin, an inhibitor of prolactin secretion, leading to a 10-fold decrease in the prolactin level in the blood, results in a twofold decrease in the intensity of specific staining of all cell layers of the granulosa in either type of follicle. Corpora lutea of the previous cycle have irregularly positioned luteocytes with weak and strong specific staining, the intensity of which is not changed in response to prolactin and diminishes slightly after the administration of bromocryptin. We conclude that the most intense changes in the content of prolactin receptors under the conditions of imbalance of this hormone during the periovulatory period are observed in those follicles where the oocyte did not ovulate by the time of early estrus.     

The effect of a periovulatory prolactin imbalance on prolactin receptor expression in rat ovary cell

Using the technique of immunohistochemistry in combination with cytophotometry, we have studied the effect of periovulatory hyper- and hypoprolactinemia on the expression of prolactin receptors in various cell types of rat ovaries during early estrus. It has been shown that intense specific staining of oocytes is positively controlled by prolactin. The maximal intensity of specific staining was found in cells of the cumulus and the inner layer of granulosa cells in mature follicles; staining intensity gradually diminished towards the outer boundary cell layer. Postovulatory follicles are distinct from those mature follicles in which there was no ovulation in their more intense manifestation of prolactin receptors in cells of the inner layer and cumulus, as well as in increased positive staining (after prolactin administration) only in the granulosa layer cells closest to theca. In follicles which did not ovulate by the time of the early estrus, prolactin administration leads to a proportional growth of specific immunoreactivity in all cell layers of the granulosa. The administration of bromocryptin, an inhibitor of prolactin secretion, leading to a 10-fold decrease in prolactin level in blood, results in a twofold decrease in the intensity of specific staining of all cell layers of the granulosa in either type of follicle. Corpora lutea of the previous cycle have irregularly positioned luteocytes with weak and strong specific staining, the intensity of which is not changed in response to prolactin and diminishes slightly after the administration of bromocryptin. We conclude that the most intense changes in the content of prolactin receptors under the conditions of imbalance of this hormone during the periovulatory period are observed in those follicles where the oocyte did not ovulate by the time of early estrus.     

Inhibition of prolactin secretion and androgenic function in the adult male rat

The effects of bromocriptine induced hypoprolactinemia on the testicular function were studied in adult rats. Bromocriptine treatment (1500 micrograms/day for 24 days) reduced serum and pituitary Prolactin levels, indicating a decrease in prolactin secretion and synthesis. No change in reproductive organ weights was seen in treated animals. Hypoprolactinemia had no effect on plasma testosterone or androstenedione levels and testicular androstenedione content, but decreased significantly testicular testosterone content. These findings indicated that experimental hypoprolactinemia induced a decrease in testicular testosterone content without affecting androgens levels.     

Differential responses of targeted lung redox enzymes to rat exposure to 60 or 85% oxygen

Rat exposure to 60% O(2) (hyper-60) or 85% O(2) (hyper-85) for 7 days confers susceptibility or tolerance, respectively, of the otherwise lethal effects of exposure to 100% O(2). The objective of this study was to determine whether activities of the antioxidant cytosolic enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1) and mitochondrial complex III are differentially altered in hyper-60 and hyper-85 lungs. Duroquinone (DQ), an NQO1 substrate, or its hydroquinone (DQH(2)), a complex III substrate, was infused into the arterial inflow of isolated, perfused lungs, and the venous efflux rates of DQH(2) and DQ were measured. Based on inhibitor effects and kinetic modeling, capacities of NQO1-mediated DQ reduction (V(max1)) and complex III-mediated DQH(2) oxidation (V(max2)) increased by ～140 and ～180% in hyper-85 lungs, respectively, compared with rates in lungs of rats exposed to room air (normoxic). In hyper-60 lungs, V(max1) increased by ～80%, with no effect on V(max2). Additional studies revealed that mitochondrial complex I activity in hyper-60 and hyper-85 lung tissue homogenates was ～50% lower than in normoxic lung homogenates, whereas mitochondrial complex IV activity was ～90% higher in only hyper-85 lung tissue homogenates. Thus NQO1 activity increased in both hyper-60 and hyper-85 lungs, whereas complex III activity increased in hyper-85 lungs only. This increase, along with the increase in complex IV activity, may counter the effects the depression in complex I activity might have on tissue mitochondrial function and/or reactive oxygen species production and may be important to the tolerance of 100% O(2) observed in hyper-85 rats.     

Effect of hypo and hyperprolactinemia on the testicular maturation of Wistar rats during puberal transition

In Wistar rats, the structural and metabolic organization of the testis was influenced by the blood concentration of prolactin. The androgen dependent enzyme activities in plasma as well as in testis were higher under hyperprolactinemia and lower under hypoprolactinemia, as induced by bromocriptine. While prolactin had direct effect on the testicular functions, bromocriptine seemed to exert its influence through blocking hypophysial prolactin.     

The giant tadpole of Pseudis paradoxa

Pseudis paradoxa has an extremely large tadpole with a long, deep tail- These features are also found in overwintering tadpoles of temperate species where low temperatures delay development and prolong prolactin exposure. Pseudis paradoxa does not occur in localities with marked seasonal temperature fluctuations. Low temperature cannot be implicated in the development of the tadpole. However, the parallels in shape between Pseudis tadpoles and those of temperate overwintering species suggest that Pseudis tadpoles may have a prolonged exposure to prolactin, higher levels of prolactin during development or an increased sensitivity to prolactin.     

Endocrine,paracrine and autocrine actions of prolactin on immune cells

The immune response is regulated by locally released factors, collectively referred to as cytokines. Data on the human immune system have convincingly demonstrated that the hormone prolactin (PRL), in addition to exerting its endocrine control on the immune system, acts as a cytokine in that it is released within the immune system and regulates the lymphocyte response by paracrine and autocrine mechanisms. Both lymphocyte and pituitary PRLs are under the control of immune factors. Synthesis of human PRL by lymphocytes is induced by T-cell stimuli, while increased release of PRL by the pituitary, observed in vivo after immune challenge, may be mediated by cytokines produced by monocyte-macrophages. Since hyperprolactinemia and hypoprolactinemia are both immunosuppressive, physiological levels of circulating PRL must be necessary to maintain basal immunocompetence. The effects of Cyclosporin (CsA) on IL-2 and PRL gene activation and the analysis of the intracellular signaling events downstream IL-2 and PRL receptors suggest coordinate actions of these two cytokines during T cell activation.     

Role of glutathione in lung retention of 99mTc-hexamethylpropyleneamine oxime in two unique rat models of hyperoxic lung injury

Rat exposure to 60% oxygen (O(2)) for 7 days (hyper-60) or to >95% O(2) for 2 days followed by 24 h in room air (hyper-95R) confers susceptibility or tolerance, respectively, of the otherwise lethal effects of subsequent exposure to 100% O(2). The objective of this study was to determine if lung retention of the radiopharmaceutical agent technetium-labeled-hexamethylpropyleneamine oxime (HMPAO) is differentially altered in hyper-60 and hyper-95R rats. Tissue retention of HMPAO is dependent on intracellular content of the antioxidant GSH and mitochondrial function. HMPAO was injected intravenously in anesthetized rats, and planar images were acquired. We investigated the role of GSH in the lung retention of HMPAO by pretreating rats with the GSH-depleting agent diethyl maleate (DEM) prior to imaging. We also measured GSH content and activities of mitochondrial complexes I and IV in lung homogenate. The lung retention of HMPAO increased by ～50% and ～250% in hyper-60 and hyper-95R rats, respectively, compared with retention in rats exposed to room air (normoxic). DEM decreased retention in normoxic (～26%) and hyper-95R (～56%) rats compared with retention in the absence of DEM. GSH content increased by 19% and 40% in hyper-60 and hyper-95R lung homogenate compared with normoxic lung homogenate. Complex I activity decreased by ～50% in hyper-60 and hyper-95R lung homogenate compared with activity in normoxic lung homogenate. However, complex IV activity was increased by 32% in hyper-95R lung homogenate only. Furthermore, we identified correlations between the GSH content in lung homogenate and the DEM-sensitive fraction of HMPAO retention and between the complex IV/complex I activity ratio and the DEM-insensitive fraction of HMPAO retention. These results suggest that an increase in the GSH-dependent component of the lung retention of HMPAO may be a marker of tolerance to sustained exposure to hyperoxia.     

Prolactin-Brain Interactions and Reproductive Function

SYNOPSIS. There is mounting evidence that prolactin influencesreproductive function in several vertebrate species via directaction on the central nervous system. In most instances, however,the basic properties of these prolactin-induced alterationsin brain function, the neurochemical mechanisms underlying theseeffects, and the identity of the prolactinlike molecules thatmight normally promote these changes have yet to be adequatelycharacterized. Several properties of the prolactin-brain relationshipthat have emerged from our work in the ring dove (Streptopeliarisoria) are described in this paper and discussed in relationto similar work in other species. Receptor binding studies usingradiolabelled mammalian prolactin preparations consistentlyindicate the existence of saturable, high affinity binding sitesfor prolactin in the brains of several vertebrate species. Theapparent concentration of these sites in the diencephalon iscorroborated by recent mapping studies in rabbits, ring doves,and three song birds in which in vitro autoradiography and densitometrywas employed. Nevertheless, direct comparisons among the threesongbird species suggest some differences in the precise distributionand/or concentration of prolactin binding sites within the preoptic-hypothalamiccontinuumthat may relate to species differences in the display of prolactin-related incubation behavior and parental activities. Althoughdefinitive evidence is currently lacking, it would appear thatblood-borne prolactin gains access to binding sites in the centralnervous system and that a receptor-mediated, blood-to-cerebrospinalfluid transport process in the choroid plexus may be a majorconduit for such uptake. Recent findings from several vertebratespecies also suggest that the brain may synthesize one or moreprolactin-like molecules that could conceivably interact withthese binding sites. Direct actions of prolactin and relatedhormones on brain mechanisms underlying reproductive processesare suggested by the profound dose-dependent suppression ofgonadotropin secretion and gonadal activity in ring doves byintracerebroventricular administration of prolactin or growthhormone at doses that are below those required for significantperipheral actions. A major challenge for future investigationwill be to identify the brain site(s) at which these and othereffects of prolactin are exerted and to determine how blood-borneprolactin of pituitary origin, prolactin-like molecules of brainorigin, and growth hormone-like molecules interact with eachother and with other neurochemical systems to promote thesetypes of changes under normal physiological conditions.     

Porcine adrenal prolactin receptors: characterization, changes during neonatal development and effects of hypoprolactinemia

1. Adrenal prolactin (PRL) receptors were identified within the adrenal cortex of pigs (Sus domesticus), and found to be located specifically on isolated zona fasciculata/reticularis cells (6437 sites per cell). 2. These PRL receptors were associated with binding to [125I]-oPRL which was characterized as being time and temperature dependent, specific for PRL, saturable, of high affinity (Ka = 10(10)/M) with a single class of binding sites, and irreversible except under extreme conditions. 3. The concentrations (fmol/mg protein) of PRL receptors decreased by 35% (P less than 0.05) between 3 and 10 days of age, and subsequently remained constant until 30 days of age. Total content (fmol/paired adrenals) increased progressively (2-fold, P less than 0.05) between 3 and 30 days of age. 4. Short-term (less than 16 hr) and prolonged (7 weeks) hypoprolactinemia (46-64% of control levels, P less than 0.05) were not associated with changes in numbers of porcine adrenal unoccupied PRL receptors.     

Molecular cloning and functional characterization of a prolactin-releasing peptide homolog from Xenopus laevis

Amino acid sequences for identified prolactin (PRL)-releasing peptides (PrRPs) were conserved in mammals (>90%) or teleost fishes (100%), but there were considerable differences between these classes in the sequence (<65%) as well as in the role of PrRP. In species other than fishes and mammals, we have identified frog PrRP. The cDNA encoding Xenopus laevis prepro-PrRP, which can generate putative PrRPs, was cloned and sequenced. Sequences for the coding region showed higher identity with teleost PrRPs than mammalian homologues, but suggested the occurrence of putative PrRPs of 20 and 31 residues as in mammals. The amino acid sequence of PrRP20 was only one residue different from teleost PrRP20, but shared 70% identity with mammalian PrRP20s. In primary cultures of bullfrog (Rana catesbeiana) pituitary cells, Xenopus PrRPs increased prolactin concentrations in culture medium to 130–160% of the control, but PrRPs was much less potent than thyrotropin-releasing hormone (TRH) causing a three- to four-fold increase in prolactin concentrations. PrRP mRNA levels in the developing Xenopus brain peak in early prometamorphosis, different from prolactin levels. PrRP may not be a major prolactin-releasing factor (PRF), at least in adult frogs, as in mammals.     

Role of prolactin on Leydig, Sertoli and germ cellular neutral lipids in bonnet monkeys, Macaca radiata.

To elucidate the specific influence of prolactin on neutral lipids in Leydig, Sertoli and germ cell compartments of the testis in immature and mature monkeys, the present study was carried out by injecting ovine prolactin (oPRL) (1 mg/kg body weight/twice daily for 10 days ip), to both age groups. Similarly, bromocryptine (an ergot alkaloid which inhibits prolactin secretion) was given to other sets of immature and mature monkeys (1 mg/kg body weight/twice daily for 10 days ip) to induce hypoprolactinemia. It was observed that after oPRL administration the total lipid accumulated in the germ cells of immature and mature monkeys. Total lipid was markedly decreased in the Leydig cells of mature monkeys only. But no such influence of PRL was evident in the Leydig cells of immature monkeys, suggesting an age-dependent effect of PRL on the Leydig cells. The increase in total lipid in the germ cells following PRL treatment was contributed by mono, di- and triacyl glycerols and free cholesterol. However, an opposite effect of PRL was evident in the Leydig cells of mature monkeys, where the cholesterols and glyceride fractions registered a decrease. The reduced cholesterol fractions in the Leydig cells following PRL treatment suggests the utilization of cholesterol for steroidogenesis. Sertoli cells were found to be comparatively resistant to change in PRL status. Bromocryptine treatment brought about the opposite effect of PRL in almost all parameters studied in both immature and mature monkeys. In general, these findings with prolactin suggests that PRL has a specific and definite influence on testicular neutral lipids and the response of different cellular compartments was found to vary.     

Effect of prolactin and growth hormone on prolactin and LH receptors in the dwarf mouse.

Dwarf mice (DW/J;dw/dw) which exhibit a deficiency of prolactin and GH secretion were treated for 8 days with ovine prolactin and/or human GH (10 or 20 mug/day) and the effect on hepatic and testicular prolactin receptors was investigated. In both sexes there was a significant increase in body weight after all hormone treatments, but an increment in testicular weight was observed only after prolactin administration. Prolactin treatment increased the specific binding % of prolactin in liver membranes in females but not males, and in testicular homogenates (together with an increase in LH receptors). The results suggest that lack of prolactin but not of GH retards sexual development in these mice. Treatment with prolactin partly counteracts this deficiency, and the effect may be mediated by the induction of hepatic and testicular prolactin and LH receptors.     

Hyperprolactinemia and erectile dysfunction

Hyperprolactinemia from a pituitary adenoma is a rare cause of erectile dysfunction. Men with erectile dysfunction who are found to have a low testosterone level should have a measurement of their prolactin level. Treatment consists of lowering the prolactin level by medication or surgery, or both. Bromocriptine, a dopamine agonist, is efficacious in lowering elevated prolactin levels and can simultaneously shrink these pituitary tumors. With large tumors, transphenoidal surgery may be used to debulk/remove the tumor. Post-treatment prolactin levels can be used to monitor the efficacy of treatment.     

Effects of hyper- and hypoprolactinemia on gonadotropin secretion, rat testicular luteinizing hormone/human chorionic gonadotropin receptors and testosterone production by isolated Leydig cells

The effect of prolactin (Prl) on gonadotropin secretion, testicular luteinizing hormone (LH)/human chorionic gonadotropin (hCG) receptors, and testosterone (T) production by isolated Leydig cells has been studied in 60-day-old rats treated for 4 days, 4 and 8 weeks with sulpiride (SLP), a dopaminergic antagonist, or for 4 days and 4 weeks with bromocriptine (CB), a dopaminergic agonist. Plasma Prl concentrations were significantly greater in the SLP groups (204 +/- 6 ng/ml) and lower in the CB groups (3.0 +/- 0.2 ng/ml) than those measured in the control groups (54 +/- 6 ng/ml). The plasma concentrations of gonadotropin were not affected by a 4-day treatment with SLP or CB, nor were they after a 4-week treatment with CB. However, the hyperprolactinemia induced by an 8-week treatment with SLP was associated with a reduced secretion of gonadotropin (LH, 16 +/- 4 vs. 35 +/- 6 ng/ml; FSH, 166 +/- 12 vs. 307 +/- 14 ng/ml). In SLP-induced hyperprolactinemia, a 30% increase in the density of the LH/hCG testicular binding sites was observed (178 +/- 12 fmol/mg protein), whereas a 60% decrease was measured in hypoprolactinemia (55 +/- 5 vs. control 133 +/- 5 fmol/mg protein). Plasma T levels were increased in 4-day and 4-week hyperprolactinemic animals (4.3 +/- 0.4 and 3.9 +/- 0.4 ng/ml, respectively), but returned to normal levels in the 8-week group (3.0 +/- 0.5 vs. C: 2.3 +/- 0.2 ng/ml). No T modifications were observed in hypoprolactinemic animals. Two distinct populations of Leydig cells (I and II) were obtained by centrifugation of dispersed testicular cells on a 0-45% continuous Metrizamide gradient. Both possess LH/hCG binding sites. However, the T production from Leydig cells of population II increased in the presence of hCG, whereas that of cell population I which also contain immature germinal cells did not respond. The basal and stimulated T secretions from cell populations I and II obtained from CB-treated animals were similar to controls, whereas from 4 days to 8 weeks of hyperprolactinemia, basal and hCG induced T productions from cell population II decreased progressively. These data show that hyperprolactinemia causes, in a time-dependent manner, a trophic effect on the density of LH/hCG testicular receptors; reduces basal and hCG-stimulated T production from isolated Leydig cells type II; and results in an elevated plasma T concentration which decreases with time. The latter suggests a slower T catabolism and/or an impaired peripheral conversion of T into 5 alpha-dihydrotestosterone (DHT). Although hypoprolactinemia is associated with a marked reduction in testicular LH receptors, it does not affect T production.     

Radioimmunoassay for ovine, caprine and bovine prolactin in plasma and tissue extracts

1. A radioimmunoassay for ovine prolactin is described based on the inhibition of the reaction between (131)I-labelled ovine prolactin and guinea-pig or rabbit antiserum to ovine prolactin. The extent of the reaction after a 4-day incubation period is determined by chromatoelectrophoresis or by adsorption of unchanged (131)I-labelled ovine prolactin on charcoal. The sensitivity is equal to 5.9ng. of prolactin/ml. of plasma with chromatoelectrophoresis, or 0.2ng. of prolactin/ml. of tissue extracts with the charcoal separation. 2. A complete cross-reaction demonstrated between ovine prolactin and caprine pituitary extracts allows the assay to be used to measure caprine prolactin. The partial cross-reactions between ovine prolactin and bovine prolactin and between ovine prolactin and bovine pituitary extract differ, and an alteration in the immunological activity of bovine prolactin during its isolation is suggested. Bovine prolactin in plasma may be measured against a bovine pituitary extract as standard. No cross-reactions were demonstrated with pituitary extracts from a number of other species. The extent of the contamination of ovine and bovine growth hormone preparations by their respective prolactins is shown. 3. Dilutions of ovine and caprine plasma inhibit the reaction between (131)I-labelled ovine prolactin and antiserum with the same characteristics as ovine prolactin. 4. The immunoreactive material in plasma fractionates on Sephadex G-200 and in sucrose density gradients as a single peak similar to that shown by freshly dissolved ovine prolactin. There is no evidence that ovine prolactin is bound to a plasma protein. 5. By suppressing prolactin secretion and assaying serial samples of plasma thereafter it is shown that the immunological activity of the surviving hormone becomes progressively altered with time. It is suggested that this alteration is usually not detected but introduces an element of uncertainty into the quantitative but not the qualitative value of the measurements obtained by reference to standard ovine prolactin.     

Effect of serotonin depletion by p-chlorophenylalanine on serum prolactin levels in estrogen-treated ovariectomized rats: insights concerning the serotoninergic, dopaminergic and opioid systems.

The stimulatory effect of serotonin on prolactin secretion is well documented, and the administration of an inhibitor of serotonin synthesis (p-chlorophenylalanine - pCPA) has the expected inhibitory action on prolactin release in most experimental situations. However, there is evidence that in certain physiological or experimental conditions, activation of the serotoninergic system can also determine inhibition of prolactin secretion. The aim of the present study was to investigate the ability of estrogen to modify the effect of pCPA on prolactin secretion and to evaluate the participation of opioid and/or dopaminergic systems in regulating pCPA-induced prolactin secretion in estradiol-treated rats. We observed that pCPA administration (200 mg/kg/day, s.c., 2 days) to ovariectomized (OVX) female rats treated with estradiol benzoate (300 microg/week for 2 weeks, or 50 microg/week for 4 weeks, s.c.) causes a significant increase in serum prolactin, whereas no effect is observed in intact rats or in OVX rats without treatment. Bromocriptine administration completely reversed prolactin values previously increased by estradiol and by pCPA [OVX rats + estradiol = 86.50 ng/ml (68.90-175.02), OVX + estradiol + pCPA = 211.30 ng/ml (142.03-311.00), OVX + estradiol + pCPA + bromocriptine = 29.35 ng/ml (23.01 - 48.74), p<0.05. Naloxone administration partially reduced estrogen-induced high prolactin concentrations, but did not affect prolactin secretion stimulation determined by pCPA. Overall, the data from this report confirm the involvement of the dopaminergic system and, to a lesser degree, of endogenous opioids in prolactin secretion stimulation determined by estradiol. Furthermore, our results suggest that the stimulatory action of pCPA on prolactin secretion in estradiol-treated OVX rats is mediated by serotonin, which may also act indirectly on dopamine neurons.     

Prolactin levels of fathers and helpers related to alloparental care in common marmosets, Callithrix jacchus

Previous studies have suggested that prolactin may play a role in regulating allocare behaviour in cotton-top tamarins, Saguinus oedipus. In this study, we investigate the prolactin profile of 3 groups of captive common marmosets, Callithrix jacchus. Carrying behaviour in this species was observed after parturition. Prolactin assays of blood samples of both fathers and helpers (sub-adult non-fathers) in 3 family groups were taken for 8 weeks before and after birth of the infants. The after-birth condition was divided into 2 groups: carrying and non-carrying animals. The results suggest a relationship between prolactin levels and allocare behaviour, with carrying behaviour being associated with increased prolactin in both fathers and helpers. This suggests that extra prolactin is produced in response to physical contact, and may be associated with carrying behaviour. Also, prolactin production may be related to learning parental skills in Neotropical primates.     

Effects of physiological and abnormally elevated prolactin levels on the pituitary-testicular axis

Prolactin can influence testicular function both directly, and indirectly via altering release of gonadotropins from the pituitary. Although numerous effects of prolactin on male reproductive functions have been described, only a few were demonstrated in more than one species. These include effects on male accessory reproductive glands, on testicular luteinizing hormone receptors, on the release of gonadotropins and on sexual behavior. In rodents, prolactin appears to play a physiological role in the pituitary regulation of testicular function. This is especially pronounced in the golden hamster. In this seasonally-breeding species, alteration of prolactin release is one of the mechanisms mediating the effects of photoperiod on the testis. In the hamster, prolactin is required for the maintenance of luteinizing hormone and prolactin receptors in the testis and treatment with prolactin can completely reverse testicular atrophy induced by exposure to short photoperiod. In both men and rats, excessive release of prolactin (hyperprolactinemia) leads to suppression of sexual behavior and gonadotropin release. These effects appear to be due to the action of prolactin on the central nervous system. Most, if not all, of the effects of prolactin exhibit striking variability among species. Moreover, prolactin can exert differential effects on the same target tissue in the same species, depending primarily on the dose.