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Start studying 9 hormones secreted from pituitary need to know what part of pit. What factors, conditions, hormones, stimulate their release. Need to know target tissues and induced responses Need to know all feedback loops to pit and hyp. Need to know cause, symptoms, and treatments of all disease we cover in class Test #2 __________ Mammary growth and Dev’t Lactogenesis __________ Roles in Vertebrates Role in non pregnant females and males 19__-shown pit extract could stimulate milk production in rabbits __________stimulate PRL directly Hyperprolactinemia and PRL secreting pit tumors are common in women of reproductive age Serum ____ increase at puberty ( FSH and LH) PROLACTIN Effects growth and differentiation of _______ __________ Hair and __________ glands in mammals Brood patch/__________ Devt in birds Evidence to suggest a role in testicular function Hypophosectomy of adult rats causes a loss of ____________ receptors and loss of testes response to LH PRL needed for __________ PROLACTIN Plasma levels only a bit higher in women ___________of conc. ranges in sexes Secreted __________ Half life in blood of ________ min Night time surge (like GH) ____________ to GH surge PROLACTIN Found _________in pit. and plasma CHO groups vary among species- this heterogeneity accounts ______ ____________ Similar to GH, but different actions Breast feeding women-________GH Acromegaly only occasionally have _________ PROLACTIN All cells express ______ receptors although the anterior pituitary is the major source of prolactin, the hormone is synthesized and secreted in _____________. Overall, several __________different actions have been reported for _________in various species. PRL critical role of prolactin in ________ has been confirmed in mice with targeted deletions in the prolactin gene. Female mice that are ________for the deleted prolactin gene (and produce roughly half the normal amount of prolactin) show failure to lactate after their first pregnancy. PROLACTIN Prolactin also appears important in several non-lactational aspects of _____________ In some species (rodents, dogs, skunks), prolactin is necessary for maintenance of _____________ (ovarian structures that secrete progesterone). PROLACTIN Mice that are __________ for an inactivated prolactin gene and thus incapable of secreting prolactin are i_________ due to defects in ovulation, fertilization, preimplantation development and implantation. PROLACTIN Effects on Immune Function The PRL receptor is widely expressed by ________cells, and some types of lymphocytes synthesize and secrete PRL. These observations suggest that _____ may act as an autocrine or paracrine modulator of immune activity. Interestingly, mice with homozygous deletions of the PRL gene ___________ significant abnormalities in immune responses. PROLACTIN Effects on Immune Function A considerable amount of research is in progress to delineate the role of PRL in normal and pathologic immune responses. It appears that prolactin has a__________role in several aspects of immune function, but is not ____________ for these responses. PROLACTIN Control of Prolactin Secretion In contrast to what is seen with all the other pituitary hormones, ________________________ suppresses prolactin secretion from the pituitary. There is usually a hypothalamic “_______" set on the lactotroph, and prolactin is secreted only when the brake is released. PROLACTIN Control of Prolactin Secretion If the pituitary stalk is cut, prolactin secretion __________, while secretion of all the other pituitary hormones ______dramatically due to loss of hypothalamic releasing hormones. PROLACTIN Control of Prolactin Secretion Dopamine serves as the major ________-inhibiting factor or brake on prolactin secretion. Dopamine is secreted into portal blood by hypothalamic neurons, binds to receptors on lactotrophs, and inhibits both the synthesis and secretion of ____________ PROLACTIN Control of Prolactin Secretion Agents and drugs that interfere with ________ secretion or receptor binding lead to __________ secretion of prolactin. PROLACTIN In addition to tonic inhibition by dopamine, PRL secretion is positively regulated by several hormones, including _____ and _______. Stimulation of the _______ and mammary gland, as occurs during nursing, leads to prolactin release. PROLACTIN _________ provide a well-studied positive control over prolactin synthesis and secretion. The increasing blood concentrations of estrogen during late pregnancy appear responsible for the elevated levels of prolactin that are necessary to prepare the mammary gland for lactation at the end of gestation. What Is a Prolactinoma? benign tumor of the pituitary gland that produces PRL ____________ type of pituitary tumor. Symptoms of prolactinoma are caused by too much _________in the blood (hyperprolactinemia) or by pressure of the tumor on surrounding tissues. How Common Is Prolactinoma? Autopsy studies indicate that ____% of the U.S. population have small pituitary tumors. _______ percent of these pituitary tumors produce prolactin, but most are not considered clinically significant. Clinically significant pituitary tumors affect the health of approximately 14 out of 100,000 people. What Causes Prolactinoma? Although research continues to unravel the mysteries of disordered cell growth-the cause of pituitary tumors ________________________. Most pituitary tumors are sporadic— they are not ____________ passed from parents to offspring. What Are the Symptoms? In women, high blood levels of PRL often cause _________________________________________. In some women, periods may disappear altogether. In others, periods may become irregular or menstrual flow may change. Women who are not pregnant or nursing may begin ________________________________. Some women may experience a loss of libido (interest in sex). Intercourse may become painful because of _________________________. What Are the Symptoms? In men, the most common symptom of prolactinoma is ___________. Because men have no reliable indicator such as menstruation to signal a problem, many men delay going to the doctor until they have headaches or eye problems caused by the enlarged pituitary pressing against nearby eye nerves. They may not recognize a gradual loss of sexual function or libido. Only after treatment do some men realize they had a problem with sexual function. What Else Causes Prolactin To Rise? In some people, high blood levels of prolactin can be traced to causes other than a pituitary tumor. __________________ -PRL secretion in the pituitary is normally suppressed by dopamine. Drugs that block the effects of ______ at the pituitary or deplete ______stores in the brain may cause the pituitary to secrete prolactin. What Else Causes Prolactin To Rise? In some people, high blood levels of prolactin can be traced to causes other than a pituitary tumor. These drugs include the major tranquilizers trifluoperazine (Stelazine) and haloperidol (Haldol); metoclopramide (Reglan), used to treat gastroesophageal reflux and the nausea caused by certain cancer drugs; and less often, alpha methyldopa and reserpine, used to control What Else Causes Prolactin To Rise? In some people, high blood levels of prolactin can be traced to causes other than a pituitary tumor. __________Pituitary Tumors Other tumors arising in or near the pituitary—such as those that cause acromegaly or Cushing's syndrome—may block the flow of ____________ from the brain to the prolactin-secreting cells. What Else Causes Prolactin To Rise? In some people, high blood levels of prolactin can be traced to causes other than a pituitary tumor. ________________ Increased prolactin levels are often seen in people with hypothyroidism, and doctors routinely test people with hyperprolactinemia for hypothyroidism. _____________________ also can cause a modest increase in the amount of prolactin in the blood. How is Prolactinoma Diagnosed? A doctor will test for prolactin blood levels in women with unexplained milk secretion (_________) or irregular menses or infertility, and in men with impaired sexual function and, in rare cases, milk secretion. How is Prolactinoma Diagnosed? If prolactin is high, a doctor will test _________ function and ask first about other conditions and medications known to raise prolactin secretion. The doctor will also request a MRI which is the most sensitive test for detecting pituitary tumors and determining their size. MRI scans may be repeated periodically to assess tumor progression and the effects of therapy. How is Prolactinoma Diagnosed? ___________________ (CT scan) also gives an image of the pituitary, but it is less sensitive than the ________ In addition to assessing the size of the pituitary tumor, doctors also look for damage to surrounding tissues, and perform tests to assess whether production of other pituitary hormones is normal. Depending on the size of the tumor, the doctor may request an ________ with measurement of visual fields. How Is Prolactinoma Treated? Medical Treatment goal of treatment is to return _____ secretion to normal, reduce tumor size, correct any visual abnormalities, and restore normal pituitary function. In the case of very large tumors, only partial achievement of this goal may be possible. Because _______is the chemical that normally inhibits prolactin secretion, doctors may treat prolactinoma with ___________e or cabergoline, drugs that act like __________ How Is Prolactinoma Treated? Medical Treatment This type of drug is called a __________ agonist. These drugs shrink the tumor and return prolactin levels to normal in approximately ____% of patients. Both have been approved by the FDA for the treatment of hyperprolactinemia. ____________is the only dopamine agonist approved for the treatment of infertility. Another dopamine agonist, pergolide, is available in the U.S., but is not approved for treating conditions that cause high blood levels of prolactin. How Is Prolactinoma Treated? Medical Treatment Bromocriptine treatment should not be ___________ without consulting a qualified endocrinologist. Prolactin levels often rise again in most people when the drug is discontinued. In some, however, prolactin levels remain normal, so the doctor may suggest reducing or discontinuing treatment every two years on a trial basis. How Is Prolactinoma Treated? Medical Treatment Cabergoline is also associated with side effects such as nausea and dizziness, but less common and less severe than with bromocriptine. As with bromocriptine therapy, side effects may be avoided if treatment is started slowly. How Is Prolactinoma Treated? Surgery Surgery should be considered if medical therapy cannot be tolerated or if it ______to reduce PRL levels, restore normal reproduction and pituitary function, and reduce tumor size. If medical therapy is only partially successful, this therapy should continue, possibly combined with surgery or radiation. The results of surgery depend a great deal on tumor size and PRL level as well as the skill and experience of the neurosurgeon. How Is Prolactinoma Treated? Surgery The________the prolactin level, the lower the chance of normalizing serum prolactin. In the best medical centers, surgery corrects prolactin levels in 80% of patients with a serum PRL less than 250 ng/ml. Even in patients with large tumors that cannot be completely removed, drug therapy may be able to return serum prolactin to the normal range after surgery. Depending on the size of the tumor and how much is removed, studies show that 2050 % will recur, usually within __ years. How do I choose a skilled neurosurgeon? Because the results of surgery are so dependent on the skill and knowledge of the neurosurgeon, a patient should ask the surgeon about the number of operations he or she has performed to remove pituitary tumors, and for success and complication rates in comparison to major medical centers. The best results come from surgeons who have performed many ___________________________ of such operations. How Does Prolactinoma Affect Pregnancy and Oral Contraceptives? If a woman has a small prolactinoma, there is no reason that she cannot conceive/have a normal pregnancy after successful medical therapy. The pituitary enlarges and prolactin production increases during normal pregnancy in women _____________ ____ How Does Prolactinoma Affect Pregnancy and Oral Contraceptives? Women with _____-secreting tumors may experience further pituitary enlargement and must be closely monitored during pregnancy. However, damage to the pituitary or eye nerves occurs in less than __% of pregnant women with prolactinoma. In women with large tumors, the risk of damage to the pituitary or eye nerves is greater, and some doctors consider around 25%